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Volume 21,Issue 2,2014 Table of Contents
2014, 21(2):119-124.
DOI: 10.3872/j.issn.1007-385X.2014.02.001
Abstract:
Viruses have been used in the treatment of cancers for more than 100 years. As the understanding of various oncolytic viruses deepens, it is more feasible to perform targeted manipulation of viral genes and thus control their behaviors and functions. Since the report of gene-modification of herpes simplex virus type 1 (HSV-1) in 1991, multi-gene recombination of oncolytic viruses (e.g. adenovirus and vaccinia virus) has been attempted. To date, more than 100 clinical trials on the application of wild-type, genetically modified or naturally mutated oncolytic viruses in cancer therapy have been registered worldwide; some of these trials have been completed while others are still ongoing. Overall, the use of oncolytic viruses for most of the common cancers evaluated has been demonstrated to be safe and encouraging clinical outcomes have been obtained. In this review paper, we attempt to outline the past achievements made from, the currently existing problems with, and the future directions and perspectives of clinical trials on oncolytic viruses in cancer therapy.
Viruses have been used in the treatment of cancers for more than 100 years. As the understanding of various oncolytic viruses deepens, it is more feasible to perform targeted manipulation of viral genes and thus control their behaviors and functions. Since the report of gene-modification of herpes simplex virus type 1 (HSV-1) in 1991, multi-gene recombination of oncolytic viruses (e.g. adenovirus and vaccinia virus) has been attempted. To date, more than 100 clinical trials on the application of wild-type, genetically modified or naturally mutated oncolytic viruses in cancer therapy have been registered worldwide; some of these trials have been completed while others are still ongoing. Overall, the use of oncolytic viruses for most of the common cancers evaluated has been demonstrated to be safe and encouraging clinical outcomes have been obtained. In this review paper, we attempt to outline the past achievements made from, the currently existing problems with, and the future directions and perspectives of clinical trials on oncolytic viruses in cancer therapy.
2014, 21(2):125-129.
DOI: 10.3872/j.issn.1007-385X.2014.02.002
Abstract:
Objective : To evaluate the regulatory effects of E2F1 on transcription factor dimerization partner-3 ( TFDP3 ) expression and apoptosis in prostate cancer cells in vitro. Methods: A luciferase reporter construct driven by the human TFDP3 gene promoter, pGL3-TFDP3-promoter, was made through PCR and subcloning using the total DNA extracted from human prostate cancer PC3 cells. PC3 cells were transfected with pGL3-TFDP3-promoter and pCMV-E2F1-HA E2F1 expression vector, either alone or together. TFDP3 promoter activity and TFDP3 protein content in the transfectants were determined by dual luciferase assays and Western blotting analysis, respectively, 48 h after transfection, while apoptosis was analyzed by flow cytometry 24 h after transfection. Results: The luciferase activity was significantly higher in PC3 cells co-transfected with pGL3-TFDP3-promoter and pCMV-E2F1-HA than PC3 cells transfected with pGL3-TFDP3-promoter alone (1.14 vs 0.61, P<0.05). TFDP3 protein content in PC3 cells transfected with pCMV-E2F1-HA was 2.7 times higher than that in non-transfected cells ([0.24±0.03] vs [0.089±0.02], P<0.05). The proportion of apoptotic cells PC3 cells transfected with pCMV-E2F1-HA (7.1±0.003)% was significantly higher than that both in non-transfected PC3 cells ([2.66±0.001]% P<0.05) and in PC3 cells co-transfected with pcDNA3-TFDP3-promoter and pCMV-E2F1-HA ([4.92±0.002]% vs [7.1±0.003]%，P<0.05). Conclusion: E2F1 may enhance the TFDP3 promoter activity and upregulate TFDP3expression in prostate cancer cells. This finding suggests that E2F1 and TFDP3 may play a role in the survival/apoptosis in prostate cancer cells.
Objective : To evaluate the regulatory effects of E2F1 on transcription factor dimerization partner-3 ( TFDP3 ) expression and apoptosis in prostate cancer cells in vitro. Methods: A luciferase reporter construct driven by the human TFDP3 gene promoter, pGL3-TFDP3-promoter, was made through PCR and subcloning using the total DNA extracted from human prostate cancer PC3 cells. PC3 cells were transfected with pGL3-TFDP3-promoter and pCMV-E2F1-HA E2F1 expression vector, either alone or together. TFDP3 promoter activity and TFDP3 protein content in the transfectants were determined by dual luciferase assays and Western blotting analysis, respectively, 48 h after transfection, while apoptosis was analyzed by flow cytometry 24 h after transfection. Results: The luciferase activity was significantly higher in PC3 cells co-transfected with pGL3-TFDP3-promoter and pCMV-E2F1-HA than PC3 cells transfected with pGL3-TFDP3-promoter alone (1.14 vs 0.61, P<0.05). TFDP3 protein content in PC3 cells transfected with pCMV-E2F1-HA was 2.7 times higher than that in non-transfected cells ([0.24±0.03] vs [0.089±0.02], P<0.05). The proportion of apoptotic cells PC3 cells transfected with pCMV-E2F1-HA (7.1±0.003)% was significantly higher than that both in non-transfected PC3 cells ([2.66±0.001]% P<0.05) and in PC3 cells co-transfected with pcDNA3-TFDP3-promoter and pCMV-E2F1-HA ([4.92±0.002]% vs [7.1±0.003]%，P<0.05). Conclusion: E2F1 may enhance the TFDP3 promoter activity and upregulate TFDP3expression in prostate cancer cells. This finding suggests that E2F1 and TFDP3 may play a role in the survival/apoptosis in prostate cancer cells.
2014, 21(2):130-135.
DOI: 10.3872/j.issn.1007-385X.2014.02.003
Abstract:
Objective : To construct a novel heat-inducible RNAi vector under the control of the heat shock protein 70B′ (HSP70B′) promoter and to examine the vector’s activities in RNAi induction and proliferation and apoptosis regulation in MCF-7 cells under the condition of heat shock. Methods: An HSP70B′ promoter-driven heat-inducible RNAi vectors against telomerase reverse transcriptase (TERT), pHSP-shTERT, was constructed through PCR-amplification of the HSP70B′ promoter and subsequent subcloning. MCF cells were optimally transfected with this vector with GFP as an indicator and flow cytometric analysis as a confirmatory assay. Untransfected MCF-7 cells were used as a control. TERT mRNA and protein levels were analyzed by RT-PCR and Western blotting, respectively. Cell proliferation and apotosis were determined by MTT assay and flow cytometry, respectively. Results: As compared with control cells, cells transfected with newly constructed vector pHSP-shTERT had significantly lower levels of TERT mRNA ([12.24±1.96]% vs \[80.18±2.28\]%; t=-286.5, P=0.000 012) and protein ([1.64±0.42]% vs [63.45±3.12]%; t=-31.37, P=0.001), significantly decreased cell viability ([58.93±2.95]% vs [91.22±4.16]%; t=15.747, P=0.004) and significantly higer apoptosis rate (\[40.97±4.80\]% vs [8.33±1.14]; t=-11.672, P=0.007). Conclusions: The novel heat inducible vector pHSP-shTERT constructed against TERT was effective to silence the TERT gene and suppress the proliferation and induce the apoptosis of MCF-7 cells under the condition of heat shock.
Objective : To construct a novel heat-inducible RNAi vector under the control of the heat shock protein 70B′ (HSP70B′) promoter and to examine the vector’s activities in RNAi induction and proliferation and apoptosis regulation in MCF-7 cells under the condition of heat shock. Methods: An HSP70B′ promoter-driven heat-inducible RNAi vectors against telomerase reverse transcriptase (TERT), pHSP-shTERT, was constructed through PCR-amplification of the HSP70B′ promoter and subsequent subcloning. MCF cells were optimally transfected with this vector with GFP as an indicator and flow cytometric analysis as a confirmatory assay. Untransfected MCF-7 cells were used as a control. TERT mRNA and protein levels were analyzed by RT-PCR and Western blotting, respectively. Cell proliferation and apotosis were determined by MTT assay and flow cytometry, respectively. Results: As compared with control cells, cells transfected with newly constructed vector pHSP-shTERT had significantly lower levels of TERT mRNA ([12.24±1.96]% vs \[80.18±2.28\]%; t=-286.5, P=0.000 012) and protein ([1.64±0.42]% vs [63.45±3.12]%; t=-31.37, P=0.001), significantly decreased cell viability ([58.93±2.95]% vs [91.22±4.16]%; t=15.747, P=0.004) and significantly higer apoptosis rate (\[40.97±4.80\]% vs [8.33±1.14]; t=-11.672, P=0.007). Conclusions: The novel heat inducible vector pHSP-shTERT constructed against TERT was effective to silence the TERT gene and suppress the proliferation and induce the apoptosis of MCF-7 cells under the condition of heat shock.
2014, 21(2):136-141.
DOI: 10.3872/j.issn.1007-385X.2014.02.004
Abstract:
Objective : To investigate the antitumor effects of an monoclonal antibody (mAb) against type 1 insulin-like growth factor receptor (IGF-ⅠR) 4F2 and cisplatin, either each alone or both in combination, on the growth of ovarian carcinoma cells and xenografts. Methods: Four ovarian carcinoma cell lines (CAOV3, ES2, SKOV3 and Hey cells) were treated with a mAb against human IGF-IR 4F2 and cisplatin, each alone or both in combination. Levels of total IGF-IR protein in CAOV3, ES2, SKOV3 and Hey cells and phosphorylated IGF-IR protein in CAOV3 and SKOV3 cells were analyzed by Western blotting before and after treatments. The binding specificity of the IGF-IR 4F2 antibody to the four types ovarian carcinoma cells was assessed by flow cytometry. The inhibitory effects of treatments on the growth of ovarian cancer cells was assessed with the CCK-8 assay in vitro. To evaluate these effects in vivo, nude mice were injected with SKOV3 and CAOV3 cells, followed by drug treatment (i.e., the IGF-IR 4F2 antibody and 0.2 μg/ml cisplatin, each alone or both in combination). PBS served as a negative control. The animals were then sacrificed and their ovarian tumor size was examined. Accordingly, rates of the treatment-induced tumor growth inhibition were calculated. Results: IGF-ⅠR protein was detected in CAOV3, ES2 and SKOV3 cells. IGF-IR 4F2 antibody bound specifically to these cells and resulted in a significant decrease in IGF-IR phosphorylation (P<0.05). The combined use of the IGF-IR 4F2 antibody and cisplatin was significantly more effective than the separate use of these two drugs in inhibiting proliferation in both SKOV3 cells ([47.4±3.1]% vs [5.3±0.6]% and [30.5±4.1]%,P<0.05) and CAOV3 cells ([51.6±2.3\]% vs [8.2±1.8]% and, [28.9±2.3]%, P<0.05). In vivo, the IGF-IR 4F2 antibody and cisplatin in combination had significantly higher inhibition rates than the two drugs each by itself on tumor growth in both mice injected with SKOV3 cells([87.3±3.1]% vs[41.6±4.9]% and [28.9±5.5]%,P<0.01) and mice injected with CAOV3 cells ([86.6±3.5]% vs [42.1±7.7]%, [32.7±4.1]%, P<0.01). Conclusion: The tested anti-human IGF-IR 4F2 mAb can bind specifically to IGF-ⅠR-positive ovarian carcinoma cells and has a synergistic inhibitory effect on the growth of ovarian carcinoma cells both in vitro and vin vivo when used in combination with cisplatin.
Objective : To investigate the antitumor effects of an monoclonal antibody (mAb) against type 1 insulin-like growth factor receptor (IGF-ⅠR) 4F2 and cisplatin, either each alone or both in combination, on the growth of ovarian carcinoma cells and xenografts. Methods: Four ovarian carcinoma cell lines (CAOV3, ES2, SKOV3 and Hey cells) were treated with a mAb against human IGF-IR 4F2 and cisplatin, each alone or both in combination. Levels of total IGF-IR protein in CAOV3, ES2, SKOV3 and Hey cells and phosphorylated IGF-IR protein in CAOV3 and SKOV3 cells were analyzed by Western blotting before and after treatments. The binding specificity of the IGF-IR 4F2 antibody to the four types ovarian carcinoma cells was assessed by flow cytometry. The inhibitory effects of treatments on the growth of ovarian cancer cells was assessed with the CCK-8 assay in vitro. To evaluate these effects in vivo, nude mice were injected with SKOV3 and CAOV3 cells, followed by drug treatment (i.e., the IGF-IR 4F2 antibody and 0.2 μg/ml cisplatin, each alone or both in combination). PBS served as a negative control. The animals were then sacrificed and their ovarian tumor size was examined. Accordingly, rates of the treatment-induced tumor growth inhibition were calculated. Results: IGF-ⅠR protein was detected in CAOV3, ES2 and SKOV3 cells. IGF-IR 4F2 antibody bound specifically to these cells and resulted in a significant decrease in IGF-IR phosphorylation (P<0.05). The combined use of the IGF-IR 4F2 antibody and cisplatin was significantly more effective than the separate use of these two drugs in inhibiting proliferation in both SKOV3 cells ([47.4±3.1]% vs [5.3±0.6]% and [30.5±4.1]%,P<0.05) and CAOV3 cells ([51.6±2.3\]% vs [8.2±1.8]% and, [28.9±2.3]%, P<0.05). In vivo, the IGF-IR 4F2 antibody and cisplatin in combination had significantly higher inhibition rates than the two drugs each by itself on tumor growth in both mice injected with SKOV3 cells([87.3±3.1]% vs[41.6±4.9]% and [28.9±5.5]%,P<0.01) and mice injected with CAOV3 cells ([86.6±3.5]% vs [42.1±7.7]%, [32.7±4.1]%, P<0.01). Conclusion: The tested anti-human IGF-IR 4F2 mAb can bind specifically to IGF-ⅠR-positive ovarian carcinoma cells and has a synergistic inhibitory effect on the growth of ovarian carcinoma cells both in vitro and vin vivo when used in combination with cisplatin.
Jia Yunlong
,
Wang Yu
,
Wang Tingting
,
Duan Yuqing
,
Ma Ming
,
Wang Miao
,
Wang Hongyan
,
Liu Lihua
2014, 21(2):142-146.
DOI: 10.3872/j.issn.1007-385X.2014.02.005
Abstract:
Objective : To investigate changes in lymphocyte subsets in tumor-draining lymph nodes (TDLNs) of esophageal cancer patients and in association with tumor progression. Methods: A total of 70 TDLN specimens were collected from esophageal cancer patients who underwent esophagectomy in the Fourth Hospital of Hebei Medical University. They were categorized as metastatic and non-metastatic based on their metastatic statuses, and as early stage and advanced stage according the TNM staging. Lymphocytes were isolated sterilely from these TDLN specimens. Proportions of CD3+ T cell, CD3+CD4+ T cell, CD3+CD8+ T cell, CD3-CD19+ B cell, CD3-CD16+CD56+ NK cell and CD4+CD25+ Treg in the mixed lymphocyte preparations were analyzed by flow cytometry. The relationships between Treg and other lymphocyte subsets were examined by Pearson’s correlation test. The differences in lymphocyte subset proportions were analyzed by student t test or Mann-Whitney U test. Results: The proportion of Treg was correlated with proportions of T cells (P=0.002) and CD4+ T cells (P=0.003) but not with proportions of CD8+ T cells, B cells and NK cells ( P>0.05). Compared to the non-metastatic group, proportions of T cells (P<0.001), CD4+ T cells (P<0.001), CD8+ T cells (P=0.016) and NK cells (P=0.038) in the metastatic group were significantly decreased, while proportions of B cells (P<0.001) and Treg (P=0.018) were significantly increased and the CD4+/CD8+ T cell ratio was not significant different (P=0.687). Proportions of T cells (P<0.001), CD4+ T cells (P=0.008), CD8+ T cells (P=0.027) and NK cells (P=0.022) were significantly lower specimens but B cell (P<0.001) and Treg (P=0.043) proportions were significantly higher in the advanced stage specimens than in the early stage specimens, while difference in the CD4+/CD8+ T cell ratio was not statistically significant (P=0.770). Conclusion: The distribution of lymphocytes seems to be disordered in TDLNs of esophageal cancer patients, thereby allowing for possible lymph node metastasis and tumor progression.
Objective : To investigate changes in lymphocyte subsets in tumor-draining lymph nodes (TDLNs) of esophageal cancer patients and in association with tumor progression. Methods: A total of 70 TDLN specimens were collected from esophageal cancer patients who underwent esophagectomy in the Fourth Hospital of Hebei Medical University. They were categorized as metastatic and non-metastatic based on their metastatic statuses, and as early stage and advanced stage according the TNM staging. Lymphocytes were isolated sterilely from these TDLN specimens. Proportions of CD3+ T cell, CD3+CD4+ T cell, CD3+CD8+ T cell, CD3-CD19+ B cell, CD3-CD16+CD56+ NK cell and CD4+CD25+ Treg in the mixed lymphocyte preparations were analyzed by flow cytometry. The relationships between Treg and other lymphocyte subsets were examined by Pearson’s correlation test. The differences in lymphocyte subset proportions were analyzed by student t test or Mann-Whitney U test. Results: The proportion of Treg was correlated with proportions of T cells (P=0.002) and CD4+ T cells (P=0.003) but not with proportions of CD8+ T cells, B cells and NK cells ( P>0.05). Compared to the non-metastatic group, proportions of T cells (P<0.001), CD4+ T cells (P<0.001), CD8+ T cells (P=0.016) and NK cells (P=0.038) in the metastatic group were significantly decreased, while proportions of B cells (P<0.001) and Treg (P=0.018) were significantly increased and the CD4+/CD8+ T cell ratio was not significant different (P=0.687). Proportions of T cells (P<0.001), CD4+ T cells (P=0.008), CD8+ T cells (P=0.027) and NK cells (P=0.022) were significantly lower specimens but B cell (P<0.001) and Treg (P=0.043) proportions were significantly higher in the advanced stage specimens than in the early stage specimens, while difference in the CD4+/CD8+ T cell ratio was not statistically significant (P=0.770). Conclusion: The distribution of lymphocytes seems to be disordered in TDLNs of esophageal cancer patients, thereby allowing for possible lymph node metastasis and tumor progression.
2014, 21(2):147-152.
DOI: 10.3872/j.issn.1007-385X.2014.02.006
Abstract:
bjective : To investigate the effect of IL-27 on the proliferation and cytotoxicity of cytokine induced killer (CIK) cells derived from human peripheral blood mononuclear cells (PBMC). Methods: Monocytes were purified from PBMCs obtained from healthy adults. After being challenged with interferon-γ (IFN-γ) and anti-human CD3, the cells were radomly divided into six groups by different stimulating factors: A group (IL-2：1 000 U/ml), B group (IL-2：1 000 U/ml, IL-27：20 ng/ml), C group (IL-2：1 000 U/ml, IL-27：10 ng/ml), D group (IL-2：500 U/ml, IL-27：10 ng/ml), E group (IL-2：1 000 U/ml, IL-27：5 ng/ml), and F group (IL-2：1000 U/ml, IL-27：40 ng/ml). The morphology of the CIK cells in different groups were evaluated by inverted microscopy. The proportion of CIK cells respectively expressing CD3 +CD56 + and CD8 + were analyzed by fluorescence activating cell sorter (FACS) on days 7 , 9, 11 and 13 after treatments. The number of attached cells was counted by a computer-based cell counter. The cytotoxicity of CIK cells was determined by MTS test. Results: Compared with A, B and C groups, D group had significantly higher proportions of CD3 +CD56 + CIK cells (\[66.57±2.44\]% vs \[60.03±1.75\]%, \[5551±0.03\]%, and \[56.07±083\]%; P<0.05) and CD8 + CIK cells (\[81.67±1.97\]% vs \[70.30±2.67\]%, \[74.92±2.47\]%, and \[74.43±1.90\]%; P<0.05), and significantly higher index of cell expansion to culture median (4 811.87±23.07 vs 3 25773±91.97, 3 790.92±64.49, 4 009.85±43.08; P<0.05) on day 11 after treatments. The highest effector to target cell ratio on day 11 in D group was 40 ∶1 with a cytotoxicity rate of (76.71±221)% which was significantly higher than that in groups A, B, and C. Conclusion: In vitro, IL-27 is capable of significantly enhancing the proliferation and cytotoxicity of CIK cells in a time-dependent manner and the optimal time of incubation seems to be 11 days.
bjective : To investigate the effect of IL-27 on the proliferation and cytotoxicity of cytokine induced killer (CIK) cells derived from human peripheral blood mononuclear cells (PBMC). Methods: Monocytes were purified from PBMCs obtained from healthy adults. After being challenged with interferon-γ (IFN-γ) and anti-human CD3, the cells were radomly divided into six groups by different stimulating factors: A group (IL-2：1 000 U/ml), B group (IL-2：1 000 U/ml, IL-27：20 ng/ml), C group (IL-2：1 000 U/ml, IL-27：10 ng/ml), D group (IL-2：500 U/ml, IL-27：10 ng/ml), E group (IL-2：1 000 U/ml, IL-27：5 ng/ml), and F group (IL-2：1000 U/ml, IL-27：40 ng/ml). The morphology of the CIK cells in different groups were evaluated by inverted microscopy. The proportion of CIK cells respectively expressing CD3 +CD56 + and CD8 + were analyzed by fluorescence activating cell sorter (FACS) on days 7 , 9, 11 and 13 after treatments. The number of attached cells was counted by a computer-based cell counter. The cytotoxicity of CIK cells was determined by MTS test. Results: Compared with A, B and C groups, D group had significantly higher proportions of CD3 +CD56 + CIK cells (\[66.57±2.44\]% vs \[60.03±1.75\]%, \[5551±0.03\]%, and \[56.07±083\]%; P<0.05) and CD8 + CIK cells (\[81.67±1.97\]% vs \[70.30±2.67\]%, \[74.92±2.47\]%, and \[74.43±1.90\]%; P<0.05), and significantly higher index of cell expansion to culture median (4 811.87±23.07 vs 3 25773±91.97, 3 790.92±64.49, 4 009.85±43.08; P<0.05) on day 11 after treatments. The highest effector to target cell ratio on day 11 in D group was 40 ∶1 with a cytotoxicity rate of (76.71±221)% which was significantly higher than that in groups A, B, and C. Conclusion: In vitro, IL-27 is capable of significantly enhancing the proliferation and cytotoxicity of CIK cells in a time-dependent manner and the optimal time of incubation seems to be 11 days.
2014, 21(2):153-159.
DOI: 10.3872/j.issn.1007-385X.2014.02.007
Abstract:
Objective : To explore synergistic effects and the underlying mechanisms of liver kinase B1 ( LKB1 ) or serine-threonine kinase 11 ( STK11 ) and metformin on proliferation and apoptosis of human cervical cancer cells using the HeLa cell line as a model. Methods: A recombinant plasmid LKB1-pEGFP-n1 was constructed. HeLa cells were transfected with this construct and the mock-vehicle pEGFP-n1 respectively. Transfectants were then treated with metformin. Cell viability was assessed by MTT assays, apoptosis and cycle progression by flow cytometry, and phosphorylation of AMRK, ACC and Rb (key players in the LKB1-AMPK signaling pathway) by Western blotting, 24 h after metformin treatment. Results: Both LKB1-pEGFP-n1 and the mock-vehicle pEGFP-n1 were successfully transfected into HeLa cells. After metformin treatment, IC50 was significantly lower in cells transfected with LKB1-pEGFP-n1(2.9±0.4) mmol/L than those transfected with pEGFP-n1 (7.8±1.3) mmol/L and wild type HeLa cells (9.6±1.5) mmol/L (P<0.01), indicating a significant cell growth-inhibiting effect for LKB1. LKB1-pEGFP-n1 group showed a G1 phase arrest after treatment with metformin. In contrast, no cell cycle arrest was evident in wild type Hela cells or HeLa cells transfected with pEGFP-n1. After treatment with 15 mmol/L metformin, apoptosis rate was significantly higher in cells transfected with LKB1-pEGFP-n1 (28.6±2.3)% than that in cells transfected with pEGFP-n1 (9.6±1.6)% and wild type cells (17.8±1.9)% (P<0.05). Phosphorylation of AMPKα and ACC was increased but phosphorylation of Rb was decreased in cells transfected with LKB1-pEGFP-n1 as compared with untransfected cells and cells transfected with pEGFP-n1. Conclusion: LKB1 and metformin may affect the proliferation and apoptosis of cervical cancer cells in a coordinated manner, possibly involving the LKB1-AMPK signaling pathway.
Objective : To explore synergistic effects and the underlying mechanisms of liver kinase B1 ( LKB1 ) or serine-threonine kinase 11 ( STK11 ) and metformin on proliferation and apoptosis of human cervical cancer cells using the HeLa cell line as a model. Methods: A recombinant plasmid LKB1-pEGFP-n1 was constructed. HeLa cells were transfected with this construct and the mock-vehicle pEGFP-n1 respectively. Transfectants were then treated with metformin. Cell viability was assessed by MTT assays, apoptosis and cycle progression by flow cytometry, and phosphorylation of AMRK, ACC and Rb (key players in the LKB1-AMPK signaling pathway) by Western blotting, 24 h after metformin treatment. Results: Both LKB1-pEGFP-n1 and the mock-vehicle pEGFP-n1 were successfully transfected into HeLa cells. After metformin treatment, IC50 was significantly lower in cells transfected with LKB1-pEGFP-n1(2.9±0.4) mmol/L than those transfected with pEGFP-n1 (7.8±1.3) mmol/L and wild type HeLa cells (9.6±1.5) mmol/L (P<0.01), indicating a significant cell growth-inhibiting effect for LKB1. LKB1-pEGFP-n1 group showed a G1 phase arrest after treatment with metformin. In contrast, no cell cycle arrest was evident in wild type Hela cells or HeLa cells transfected with pEGFP-n1. After treatment with 15 mmol/L metformin, apoptosis rate was significantly higher in cells transfected with LKB1-pEGFP-n1 (28.6±2.3)% than that in cells transfected with pEGFP-n1 (9.6±1.6)% and wild type cells (17.8±1.9)% (P<0.05). Phosphorylation of AMPKα and ACC was increased but phosphorylation of Rb was decreased in cells transfected with LKB1-pEGFP-n1 as compared with untransfected cells and cells transfected with pEGFP-n1. Conclusion: LKB1 and metformin may affect the proliferation and apoptosis of cervical cancer cells in a coordinated manner, possibly involving the LKB1-AMPK signaling pathway.
2014, 21(2):160-164.
DOI: 10.3872/j.issn.1007-385X.2014.02.008
Abstract:
Objective : To investigate the effects of siRNA CD31-targeted silencing of the platelet endothelial cell adhesion molecule 1 ( PECAM-1 ) or CD31 gene on VEGF expression and proliferation in endothelial cells. Methods: Murine hemangioendothelioma cells (EOMAs) were used as a model. They were transfected with naked siRNA CD31, siRNA CD31-FAM, a stable negative control (SNC) siRNA and Opti-Med as a blank control, respectively, using lipofectamin (RNAi-mate). After transfection, cell proliferation was assessed by MTT assays. PECAM-1 and VEGF mRNA and protein levels were determined by RT-PCR and Western blotting respectively. Results: PECAM-1 mRNA and protein levels and proliferative activity were all significantly lower in EOMAs transfected with naked siRNA CD31 and siRNA CD31-FAM than in EOMAs transfected with the SNC and Opti-MEM (P<0.01). As compared with the SNC, naked siRNA CD31 and siRNA CD31-FAM rested significantly higher rates of proliferation inhibition (P<0.01). Conclusion: The chemically synthesized 2’-O-methyl-siRNA CD31 may effectively silence the target gene PECAM-1 and inhibit proliferation in EOMAs, at least partially through a VEGF signaling-dependent mechanism.
Objective : To investigate the effects of siRNA CD31-targeted silencing of the platelet endothelial cell adhesion molecule 1 ( PECAM-1 ) or CD31 gene on VEGF expression and proliferation in endothelial cells. Methods: Murine hemangioendothelioma cells (EOMAs) were used as a model. They were transfected with naked siRNA CD31, siRNA CD31-FAM, a stable negative control (SNC) siRNA and Opti-Med as a blank control, respectively, using lipofectamin (RNAi-mate). After transfection, cell proliferation was assessed by MTT assays. PECAM-1 and VEGF mRNA and protein levels were determined by RT-PCR and Western blotting respectively. Results: PECAM-1 mRNA and protein levels and proliferative activity were all significantly lower in EOMAs transfected with naked siRNA CD31 and siRNA CD31-FAM than in EOMAs transfected with the SNC and Opti-MEM (P<0.01). As compared with the SNC, naked siRNA CD31 and siRNA CD31-FAM rested significantly higher rates of proliferation inhibition (P<0.01). Conclusion: The chemically synthesized 2’-O-methyl-siRNA CD31 may effectively silence the target gene PECAM-1 and inhibit proliferation in EOMAs, at least partially through a VEGF signaling-dependent mechanism.
2014, 21(2):165-168.
DOI: 10.3872/j.issn.1007-385X.2014.02.009
Abstract:
Objective : To investigate the effect of histone deacetylase (HDAC) inhibitor MS-275 on proliferation and apoptosis in human cervical carcinoma cells as well as the mechanisms underlying the effect. Methods: The human cervical carcinoma cell line, SiHa, was used as a model. SiHa cells were treated with histone deacetylase inhibitor MS-275 at 5, 10, and 20 μmol/L, respectively, for 48 h. The cell viability was assessed by MTT assays and the rate of cell apoptosis was determined by flow cytometry. Levels of acetyl histone H4 and p21 and p53 gene transcripts were analyzed by Western blotting and RT-PCR respectively. Results: MS-275 treatment resulted in an decrease in cellular growth activity and increases in apoptosis acetyl level of histone H4 and p21 and p53 mRNA abundance in SiHa cells in a concentration-dependent manner. Conclusion: Histone deacetylase inhibition may effectively inhibit the cellular proliferation and induce apoptosis in cervical carcinoma cells. The mechanisms underlying these effects may involve increased acetylation of histone up-regulated expression of p21 and p53.
Objective : To investigate the effect of histone deacetylase (HDAC) inhibitor MS-275 on proliferation and apoptosis in human cervical carcinoma cells as well as the mechanisms underlying the effect. Methods: The human cervical carcinoma cell line, SiHa, was used as a model. SiHa cells were treated with histone deacetylase inhibitor MS-275 at 5, 10, and 20 μmol/L, respectively, for 48 h. The cell viability was assessed by MTT assays and the rate of cell apoptosis was determined by flow cytometry. Levels of acetyl histone H4 and p21 and p53 gene transcripts were analyzed by Western blotting and RT-PCR respectively. Results: MS-275 treatment resulted in an decrease in cellular growth activity and increases in apoptosis acetyl level of histone H4 and p21 and p53 mRNA abundance in SiHa cells in a concentration-dependent manner. Conclusion: Histone deacetylase inhibition may effectively inhibit the cellular proliferation and induce apoptosis in cervical carcinoma cells. The mechanisms underlying these effects may involve increased acetylation of histone up-regulated expression of p21 and p53.
10 Effects of Quercetin on the proliferation and apoptosis of human small cell lung cancer H446 cells
2014, 21(2):169-174.
DOI: 10.3872/j.issn.1007-385X.2014.02.010
Abstract:
Objective : To observe the effect of Quercetin on the apoptosis of small cell lung cancer cell lines H446, and investigate the potential mechanism. Methods: After the treatment of 100 μmol/L and 200 μmol/L quercetin 48 h, confocal microscope was introduced to observe the effect of quercetin on proliferation of H446 cell. MTT assay was used to detect the anti-proliferative effect of quercetin on H446 cells. Flow cytometry was used to detect the influence of quercetin on the cell cycle of H446 cells. The expressions of apoptosis-related proteins P53, Bcl-2 and Bax in H446 cells were determined by Western blotting. Results: After treated with quercetin, nuclear became shrinkage and was divided into a serial of apoptotic bodies as the density of H446 cell decreased. Quercetin inhibited proliferation of H446 cells in a significant dose-dependent (P<0.05) and time-dependent (P<0.05) manner. After treated with quercetin for 12, 24, 48 and 72 h , its IC50 value to H446 cells were (172.2±2.6) , (102.4±5.3), (68.6±2.7) and (48.8±1.9) μmol/L respectively. Quercetin promoted the apoptosis of H446 cells in a significant dose-dependent manner. The apoptosis rate of H446 cell in 40 μmol/L quercetin group was higher than that of the control group ([8.3±0.4]% vs [4.0±0.5]%, P<0.01). When the concentration was arrived at 200 μmol/L, the apoptosis rate achieved the highest. Quercetin caused cell cycle arrest of H446 at the G2/M phase. Compared with the control group, the expressions of P53 ([4.98±0.91] vs [0.68±0.26], P<0.01) and Bax ([4.26±0.23] vs [0.89±0.29], P<0.01) were significantly higher in 200 μmol/L quercetin group, meanwhile, the Bcl-2 expression decreased significantly ([0.36±0.06] vs [8.23±1.65], P<0.01). Conclusion: Quercetin can inhibit the proliferation of H446 cells and promote it apoptosis, and the potential mechanism is probably related with regulation of apoptosis-related proteins such as Bax, P53 and Bcl-2.
Objective : To observe the effect of Quercetin on the apoptosis of small cell lung cancer cell lines H446, and investigate the potential mechanism. Methods: After the treatment of 100 μmol/L and 200 μmol/L quercetin 48 h, confocal microscope was introduced to observe the effect of quercetin on proliferation of H446 cell. MTT assay was used to detect the anti-proliferative effect of quercetin on H446 cells. Flow cytometry was used to detect the influence of quercetin on the cell cycle of H446 cells. The expressions of apoptosis-related proteins P53, Bcl-2 and Bax in H446 cells were determined by Western blotting. Results: After treated with quercetin, nuclear became shrinkage and was divided into a serial of apoptotic bodies as the density of H446 cell decreased. Quercetin inhibited proliferation of H446 cells in a significant dose-dependent (P<0.05) and time-dependent (P<0.05) manner. After treated with quercetin for 12, 24, 48 and 72 h , its IC50 value to H446 cells were (172.2±2.6) , (102.4±5.3), (68.6±2.7) and (48.8±1.9) μmol/L respectively. Quercetin promoted the apoptosis of H446 cells in a significant dose-dependent manner. The apoptosis rate of H446 cell in 40 μmol/L quercetin group was higher than that of the control group ([8.3±0.4]% vs [4.0±0.5]%, P<0.01). When the concentration was arrived at 200 μmol/L, the apoptosis rate achieved the highest. Quercetin caused cell cycle arrest of H446 at the G2/M phase. Compared with the control group, the expressions of P53 ([4.98±0.91] vs [0.68±0.26], P<0.01) and Bax ([4.26±0.23] vs [0.89±0.29], P<0.01) were significantly higher in 200 μmol/L quercetin group, meanwhile, the Bcl-2 expression decreased significantly ([0.36±0.06] vs [8.23±1.65], P<0.01). Conclusion: Quercetin can inhibit the proliferation of H446 cells and promote it apoptosis, and the potential mechanism is probably related with regulation of apoptosis-related proteins such as Bax, P53 and Bcl-2.
2014, 21(2):175-180.
DOI: 10.3872/j.issn.1007-385X.2014.02.011
Abstract:
Objective : To determine mRNA levels and methylation status of stem cell transcription factor SRY-Box2 in gastric cancer (GC) cell lines (MKN74, MKN45) and tissue specimens in association with pathogenesis and clinicopathological features of GC. Methods: Eighty-six gastric cancer patients diagnosed in the Thoracic Surgery of the Fourth Hospital of Hebei Medical University between 2007 and 2012 were recruited. Biopsy specimens were collected from primary tumors and the corresponding adjacent tissues. The gastric cancer cell lines (MKN74, MKN45) were treated respectively with 5-aza-2’-deoxycytidine (5-Aza-Dc) and trichostatin A (TSA). Levels of CpG methylation of the SRY-Box2 promoter and SRY-Box2 mRNA were assessed by methylation specific PCR (MSP) and RT-PCR, respectively, in MKN74, MKN45 cells after drug treatments and in biopsy specimens. The relevance of SRY-Box2 gene methylation to and clinicopathological features of the cancer and to changes in RY-Box2 mRNA abundance was analyzed. Results: SRY-Box2 mRNA was detected in MKN45 cells but not in MKN74 cells. Treatment with 5-aza-2’-deoxycytidine (5-Aza-Dc, a demethylation agent) significantly increased SRY-Box2 mRNA abundance but trichostatin A (TSA) had no effect inMKN45 cells. Hypermethylation of SRY-Box2 gene containing a CpG island was observed in MKN74 cells. The frequency of expression loss of the SRY-Box2 gene (19.8% vs 7.0%; χ 2=69.073, P=0.014) and the level of hypermethylation (14.0% vs 1.2%；χ 2=10.069, P=0.002) were all significantly higher in the cancer tissue as compared with adjacent non-cancerous tissues.and hypermethylation was significantly correlated with expression loss in the SRY-Box2 gene (χ 2=50.878,P<0001). Furthermore, SRY-Box2 gene hypermethylation status was also correlated with lymph node metastasis (χ 2=3947, P=0.047), but not with clinical stage, pathological grade and depth of invasion ( P>0.05). Conclusion: CpG hypermethylation may be one of the mechanisms responsible for the expression loss of the SRY-Box2 gene and may play some role in the pathogenesis of gastric cancer.
Objective : To determine mRNA levels and methylation status of stem cell transcription factor SRY-Box2 in gastric cancer (GC) cell lines (MKN74, MKN45) and tissue specimens in association with pathogenesis and clinicopathological features of GC. Methods: Eighty-six gastric cancer patients diagnosed in the Thoracic Surgery of the Fourth Hospital of Hebei Medical University between 2007 and 2012 were recruited. Biopsy specimens were collected from primary tumors and the corresponding adjacent tissues. The gastric cancer cell lines (MKN74, MKN45) were treated respectively with 5-aza-2’-deoxycytidine (5-Aza-Dc) and trichostatin A (TSA). Levels of CpG methylation of the SRY-Box2 promoter and SRY-Box2 mRNA were assessed by methylation specific PCR (MSP) and RT-PCR, respectively, in MKN74, MKN45 cells after drug treatments and in biopsy specimens. The relevance of SRY-Box2 gene methylation to and clinicopathological features of the cancer and to changes in RY-Box2 mRNA abundance was analyzed. Results: SRY-Box2 mRNA was detected in MKN45 cells but not in MKN74 cells. Treatment with 5-aza-2’-deoxycytidine (5-Aza-Dc, a demethylation agent) significantly increased SRY-Box2 mRNA abundance but trichostatin A (TSA) had no effect inMKN45 cells. Hypermethylation of SRY-Box2 gene containing a CpG island was observed in MKN74 cells. The frequency of expression loss of the SRY-Box2 gene (19.8% vs 7.0%; χ 2=69.073, P=0.014) and the level of hypermethylation (14.0% vs 1.2%；χ 2=10.069, P=0.002) were all significantly higher in the cancer tissue as compared with adjacent non-cancerous tissues.and hypermethylation was significantly correlated with expression loss in the SRY-Box2 gene (χ 2=50.878,P<0001). Furthermore, SRY-Box2 gene hypermethylation status was also correlated with lymph node metastasis (χ 2=3947, P=0.047), but not with clinical stage, pathological grade and depth of invasion ( P>0.05). Conclusion: CpG hypermethylation may be one of the mechanisms responsible for the expression loss of the SRY-Box2 gene and may play some role in the pathogenesis of gastric cancer.
2014, 21(2):187-191.
DOI: 10.3872/j.issn.1007-385X.2014.02.013
Abstract:
Objective : To modify the classical chick embryo chorioallantoic membrane (CAM) xenograft model of tumuorigenesis and evaluate the effectiveness and feasibility of the modified model in the screening of anti-angiogenesis drugs. Methods: Fertilized chicken eggs randomized into two groups. Eggs in the classical model group were grafted with U87 human glioma cells and the anti-angiogenic activity of test drugs, thalidomide (50, 100, 200 μg/ml), G3B6 and DMSO (the control) was determined by following the well-established classical methods. In the modified model group, the CAM was given an additional adaptation period of 9-16 h and then grafted with U8 cells by inoculating the cells into a silicone ring and then placing the ring on the half of the grade 1 vessel of the CAM. The test drugs were added into the silicone ring where their anti-angiogenic activity was evaluated. For both groups, the tumor morphology and the microvessel density (MVD) in the tumor tissue were examined under a stereo microscope with photos taken. Changes in the tumor histology was assessed by H-E staining and the expression of VEGFR2, the marker of the angiogenesis, was assessed by in situ hybridization. Results: The success rate of the xenograft was increased significantly without any negative effect on angiogenesis in the CAM in the modified model as compared with the classical model (\[70±4.226\]% vs \[41.25±5154\]%; t=4.314, P=0.000 7). The tumor volume was also significantly increased in the modified model group as compared with thecalissical model group (\[60.20±6.012\] vs \[15.97±2.403\] mm 3; t=6.012, P<0.000 1). Both thalidomide and G3B6 effectively inhibited the angiogenesis and reduced the MVD and VEGFR2 expression in the tumor tissue. Conclusion: The modified xenograft CAM model of tumuorigenesis developed in this study seems superior over the classical CAM model in studying tumorigenesis and screening anti-angiogenesis drugs.
Objective : To modify the classical chick embryo chorioallantoic membrane (CAM) xenograft model of tumuorigenesis and evaluate the effectiveness and feasibility of the modified model in the screening of anti-angiogenesis drugs. Methods: Fertilized chicken eggs randomized into two groups. Eggs in the classical model group were grafted with U87 human glioma cells and the anti-angiogenic activity of test drugs, thalidomide (50, 100, 200 μg/ml), G3B6 and DMSO (the control) was determined by following the well-established classical methods. In the modified model group, the CAM was given an additional adaptation period of 9-16 h and then grafted with U8 cells by inoculating the cells into a silicone ring and then placing the ring on the half of the grade 1 vessel of the CAM. The test drugs were added into the silicone ring where their anti-angiogenic activity was evaluated. For both groups, the tumor morphology and the microvessel density (MVD) in the tumor tissue were examined under a stereo microscope with photos taken. Changes in the tumor histology was assessed by H-E staining and the expression of VEGFR2, the marker of the angiogenesis, was assessed by in situ hybridization. Results: The success rate of the xenograft was increased significantly without any negative effect on angiogenesis in the CAM in the modified model as compared with the classical model (\[70±4.226\]% vs \[41.25±5154\]%; t=4.314, P=0.000 7). The tumor volume was also significantly increased in the modified model group as compared with thecalissical model group (\[60.20±6.012\] vs \[15.97±2.403\] mm 3; t=6.012, P<0.000 1). Both thalidomide and G3B6 effectively inhibited the angiogenesis and reduced the MVD and VEGFR2 expression in the tumor tissue. Conclusion: The modified xenograft CAM model of tumuorigenesis developed in this study seems superior over the classical CAM model in studying tumorigenesis and screening anti-angiogenesis drugs.
2014, 21(2):192-202.
DOI: 10.3872/j.issn.1007-385X.2014.02.014
Abstract:
Immunologic adjuvants are compounds that can help vaccines to enhance or change the antigen-specific immune response. The vast majority of human spontaneous tumors are weakly immunogenic or non-immunogenic. Adjuvants can enhance the immunogenicity of tumor antigens, promote antigen presentation, and induce anti-tumor immune response, thus having important implications in improving the efficacy of cancer biotherapy. Adjuvants can be classified according to their functional properties and the mechanisms underlying their functional activities into three types: immunomodulatory adjuvants, antigen-deliverying adjuvants and adjuvants with immunomodulatory-antigen delivery functions. Aluminum, emulsion, virosome, cholera toxin, CpG ODN and other adjuvants have now been approved for combinational use with human vaccine(s) in clinics or clinical trials. Nevertheless, the currently available adjuvants are associated with some limitations such as suboptimal safety profiles and significant adverse effects, thus prompting for the development of novel types of safer and more efficient vaccines and adjuvants, which is becoming one of the hottest areas of translational research in immunotherapy. This review aims to summarize the characteristics of adjuvants and the mechanisms underlying their effects, present the recent advances and current status in the translational research of adjuvants, and discusse the challenges and possible trends in adjuvant development in the future.
Immunologic adjuvants are compounds that can help vaccines to enhance or change the antigen-specific immune response. The vast majority of human spontaneous tumors are weakly immunogenic or non-immunogenic. Adjuvants can enhance the immunogenicity of tumor antigens, promote antigen presentation, and induce anti-tumor immune response, thus having important implications in improving the efficacy of cancer biotherapy. Adjuvants can be classified according to their functional properties and the mechanisms underlying their functional activities into three types: immunomodulatory adjuvants, antigen-deliverying adjuvants and adjuvants with immunomodulatory-antigen delivery functions. Aluminum, emulsion, virosome, cholera toxin, CpG ODN and other adjuvants have now been approved for combinational use with human vaccine(s) in clinics or clinical trials. Nevertheless, the currently available adjuvants are associated with some limitations such as suboptimal safety profiles and significant adverse effects, thus prompting for the development of novel types of safer and more efficient vaccines and adjuvants, which is becoming one of the hottest areas of translational research in immunotherapy. This review aims to summarize the characteristics of adjuvants and the mechanisms underlying their effects, present the recent advances and current status in the translational research of adjuvants, and discusse the challenges and possible trends in adjuvant development in the future.
2014, 21(2):203-206.
DOI: 10.3872/j.issn.1007-385X.2014.2.015
Abstract:
Pomalidomide is a highly potent third-generation immunomodulatory drug (IMiD), with pharmacologic properties similar to those of the first-generation drug thalidomide. However, compared with thalidomide, pomalidomide has stronger antiangiogenic, antineoplastic, and anti-inflammatory, and anti-myeloma activities in vitro and in vivo, with less side effects and better oral tolerance. In February, 2013, pomalidomide has been approved by the U.S. Food and Drug Administration for use in the treatment of relapsed and refractory multiple myeloma (MM). This review will focus on the recent advances on the translation of pomalidomide from bench to bedside as a therapeutic agent for relapsed and refractory multiple myeloma, myelofibrosis, immunoglobulin light-chain amyloidosis (AL), small cell lung cancer (SCLC), and other advanced solid tumors.
Pomalidomide is a highly potent third-generation immunomodulatory drug (IMiD), with pharmacologic properties similar to those of the first-generation drug thalidomide. However, compared with thalidomide, pomalidomide has stronger antiangiogenic, antineoplastic, and anti-inflammatory, and anti-myeloma activities in vitro and in vivo, with less side effects and better oral tolerance. In February, 2013, pomalidomide has been approved by the U.S. Food and Drug Administration for use in the treatment of relapsed and refractory multiple myeloma (MM). This review will focus on the recent advances on the translation of pomalidomide from bench to bedside as a therapeutic agent for relapsed and refractory multiple myeloma, myelofibrosis, immunoglobulin light-chain amyloidosis (AL), small cell lung cancer (SCLC), and other advanced solid tumors.
2014, 21(2):207-209.
DOI: 10.3872/j.issn.1007-385X.2014.02.016
Abstract:
目的： 探讨抑制miRNA-21表达对宫颈癌HeLa细胞中PTEN的表达及细胞增殖、侵袭能力的影响。 方 法： 以脂质体介导anti-miRNA-21（anti-miRNA-21转染组）、anti-miRNA-21-neg（阴性对照组）转染HeLa细胞，同时设空白对照组（未转染组）。应用Real-time PCR技术检测3组细胞中miRNA-21的表达，Western blotting 检测3组细胞中PTEN的表达，MTT法检测3组细胞的增殖能力，Transwell实验检测3组细胞的侵袭能力。结果： Anti-miR-21转染组与阴性对照组相比，HeLa细胞中miRNA-21的表达量明显降低\[（0.187±0.027）vs （0.861±0.144），P＜0.01\]。转染 anti-miRNA-21 96 h后，HeLa细胞增殖抑制率明显升高\[（49.44±1.97）% vs （4.36±0.64）%，P＜0.01\]。Anti-miR-21转染组与阴性、空白对照相比， Hela细胞的侵袭细胞数明显减少\[（29.4±2.1）vs （40.4±2.9）、（41.2±2.6）个，均P＜0.01\]；PTEN蛋白的表达则明显增加\[（1766.00±35.56）vs（726.00±5.48）、（729.25±17.73），均P<0.01\]。 结论： 抑制miRNA-21的表达后，宫颈癌HeLa细胞增殖、侵袭能力明显下降，其机制可能与上调PTEN的表达有一定关系。
目的： 探讨抑制miRNA-21表达对宫颈癌HeLa细胞中PTEN的表达及细胞增殖、侵袭能力的影响。 方 法： 以脂质体介导anti-miRNA-21（anti-miRNA-21转染组）、anti-miRNA-21-neg（阴性对照组）转染HeLa细胞，同时设空白对照组（未转染组）。应用Real-time PCR技术检测3组细胞中miRNA-21的表达，Western blotting 检测3组细胞中PTEN的表达，MTT法检测3组细胞的增殖能力，Transwell实验检测3组细胞的侵袭能力。结果： Anti-miR-21转染组与阴性对照组相比，HeLa细胞中miRNA-21的表达量明显降低\[（0.187±0.027）vs （0.861±0.144），P＜0.01\]。转染 anti-miRNA-21 96 h后，HeLa细胞增殖抑制率明显升高\[（49.44±1.97）% vs （4.36±0.64）%，P＜0.01\]。Anti-miR-21转染组与阴性、空白对照相比， Hela细胞的侵袭细胞数明显减少\[（29.4±2.1）vs （40.4±2.9）、（41.2±2.6）个，均P＜0.01\]；PTEN蛋白的表达则明显增加\[（1766.00±35.56）vs（726.00±5.48）、（729.25±17.73），均P<0.01\]。 结论： 抑制miRNA-21的表达后，宫颈癌HeLa细胞增殖、侵袭能力明显下降，其机制可能与上调PTEN的表达有一定关系。
2014, 21(2):210-215.
DOI: 10.3872/j.issn.1007-385X.2014.02.017
Abstract:
结直肠癌（colorectal cancer，CRC）是常见的恶性肿瘤及肿瘤相关致死原因之一，临床上多采用以外科手术为主的多学科综合治疗策略。调节性T细胞（regulatory T cell，Treg）被认为是肿瘤免疫逃逸和免疫治疗失败的一个重要因素。近年的研究显示，叉头样转录因子3（transcription factor forkhead box P3，FOXP3）不仅是CD4 +CD25 +T细胞的重要的胞内标志，也是与其发育分化与功能发挥相关的重要因子。FOXP3 +Treg与多种人类肿瘤的生存预后存在关联，高比例的FOXP3 +Treg常与不良的临床预后存在相关。然而，新近多个研究表明，在CRC患者中，肿瘤组织中FOXP3 + Treg富集常与其更好的生存预后有关。Treg在肠道黏膜中可能通过抑制肠道细菌侵袭所引起的炎症和免疫反应，起到了正面抗肿瘤而非免疫耐受的效应。近来，Treg特定的去甲基化区域（Treg-specific demethylated region, TSDR）被认为是稳定表达FOXP3的nTreg的一个特异的表观遗传学标志，多项研究证实人类自然发生型Treg(naturally occurred Treg, nTreg)细胞上该区域呈显著的去甲基化现象。 FOXP3 -TSDR去甲基化状态检测对结直肠癌相关研究策略或许是一个重要的启发。
结直肠癌（colorectal cancer，CRC）是常见的恶性肿瘤及肿瘤相关致死原因之一，临床上多采用以外科手术为主的多学科综合治疗策略。调节性T细胞（regulatory T cell，Treg）被认为是肿瘤免疫逃逸和免疫治疗失败的一个重要因素。近年的研究显示，叉头样转录因子3（transcription factor forkhead box P3，FOXP3）不仅是CD4 +CD25 +T细胞的重要的胞内标志，也是与其发育分化与功能发挥相关的重要因子。FOXP3 +Treg与多种人类肿瘤的生存预后存在关联，高比例的FOXP3 +Treg常与不良的临床预后存在相关。然而，新近多个研究表明，在CRC患者中，肿瘤组织中FOXP3 + Treg富集常与其更好的生存预后有关。Treg在肠道黏膜中可能通过抑制肠道细菌侵袭所引起的炎症和免疫反应，起到了正面抗肿瘤而非免疫耐受的效应。近来，Treg特定的去甲基化区域（Treg-specific demethylated region, TSDR）被认为是稳定表达FOXP3的nTreg的一个特异的表观遗传学标志，多项研究证实人类自然发生型Treg(naturally occurred Treg, nTreg)细胞上该区域呈显著的去甲基化现象。 FOXP3 -TSDR去甲基化状态检测对结直肠癌相关研究策略或许是一个重要的启发。
2014, 21(2):216-219.
DOI: 10.3872/j.issn.1007-385X.2014.02.018
Abstract:
巨噬细胞是机体固有免疫反应的重要组成成份，在不同趋化因子的作用下极化为具有不同表面标志及功能的巨噬细胞。大量研究表明，肿瘤组织中的巨噬细胞为M2型，其能够促进肿瘤生长、侵袭和转移。M2型巨噬细胞在适当的诱导下可以转换为M1型。本文将近年来从HIV-1 Nef蛋白、CD40L、双磷酸盐及CpG-DNA联合IL-10R抗体等方面对巨噬细胞表型逆转的研究做一综述。巨噬细胞的表型逆转将可能为未来肿瘤治疗提供新的策略。
巨噬细胞是机体固有免疫反应的重要组成成份，在不同趋化因子的作用下极化为具有不同表面标志及功能的巨噬细胞。大量研究表明，肿瘤组织中的巨噬细胞为M2型，其能够促进肿瘤生长、侵袭和转移。M2型巨噬细胞在适当的诱导下可以转换为M1型。本文将近年来从HIV-1 Nef蛋白、CD40L、双磷酸盐及CpG-DNA联合IL-10R抗体等方面对巨噬细胞表型逆转的研究做一综述。巨噬细胞的表型逆转将可能为未来肿瘤治疗提供新的策略。
2014, 21(2):220-226.
DOI: 10.3872/j.issn.1007-385X.2014.02.019
Abstract:
低氧是造血、炎症、免疫应答耐受、组织损伤和肿瘤等过程中普遍存在的一种生理或病理现象。组织中的低氧微环境一方面能招募免疫细胞迁移到低氧组织，另一方面诱导其代谢方式切换为低氧代谢，同时改变其免疫功能。并且，肿瘤组织的低氧状态对天然免疫和适应性免疫具有不同的调控作用。本文着重对哺乳动物细胞的低氧适应机制、低氧对天然免疫和适应性免疫细胞的分化发育、功能调控及其在肿瘤发生发展过程中的作用进行综述，研究和认识肿瘤组织低氧微环境对免疫系统的功能调控也会为肿瘤治疗提供新的策略。
低氧是造血、炎症、免疫应答耐受、组织损伤和肿瘤等过程中普遍存在的一种生理或病理现象。组织中的低氧微环境一方面能招募免疫细胞迁移到低氧组织，另一方面诱导其代谢方式切换为低氧代谢，同时改变其免疫功能。并且，肿瘤组织的低氧状态对天然免疫和适应性免疫具有不同的调控作用。本文着重对哺乳动物细胞的低氧适应机制、低氧对天然免疫和适应性免疫细胞的分化发育、功能调控及其在肿瘤发生发展过程中的作用进行综述，研究和认识肿瘤组织低氧微环境对免疫系统的功能调控也会为肿瘤治疗提供新的策略。
2014, 21(2):227-230.
DOI: 10.3872/j.issn.1007-385X.2014.02.020
Abstract:
放射性抵抗是目前肿瘤放射治疗中难以解决的一大难点。放射损伤的作用靶点为DNA， DNA损伤后，会启动自身的修复系统进行修复，能针对自身不同类型的DNA损伤启动不同修复机制，DNA的修复在一定程度上导致了放疗抵抗的发生。近年来，RNA干扰在肿瘤、病毒性疾病和遗传病等基因治疗研究方面均取得了一定的成果,早在1968年，Alexander就提出了细胞辐射敏感性取决于其DNA链断裂修复能力的概念。相关研究证明，通过构建表达dsRNA或者siRNA来干扰DNA修复蛋白，如Ku二聚体(Ku70和Ku80)、DNA-PKcs、Ku、ATM、Rad51、BRCA1、P53、XRCC4等的表达，联合放疗，都在不同程度上增加了放疗的敏感性。本文就RNA干扰DNA修复促进肿瘤细胞放疗敏感性的研究进展作一综述，并对其应用于肿瘤临床治疗的前景提出展望。
放射性抵抗是目前肿瘤放射治疗中难以解决的一大难点。放射损伤的作用靶点为DNA， DNA损伤后，会启动自身的修复系统进行修复，能针对自身不同类型的DNA损伤启动不同修复机制，DNA的修复在一定程度上导致了放疗抵抗的发生。近年来，RNA干扰在肿瘤、病毒性疾病和遗传病等基因治疗研究方面均取得了一定的成果,早在1968年，Alexander就提出了细胞辐射敏感性取决于其DNA链断裂修复能力的概念。相关研究证明，通过构建表达dsRNA或者siRNA来干扰DNA修复蛋白，如Ku二聚体(Ku70和Ku80)、DNA-PKcs、Ku、ATM、Rad51、BRCA1、P53、XRCC4等的表达，联合放疗，都在不同程度上增加了放疗的敏感性。本文就RNA干扰DNA修复促进肿瘤细胞放疗敏感性的研究进展作一综述，并对其应用于肿瘤临床治疗的前景提出展望。
2014, 21(2):231-234.
DOI: 10.3872/j.issn.1007-385X.2014.02.021
Abstract:
CXCR7\[chemokine (C-X-C motif) receptor 7\]是一个近年来新发现的基质细胞衍生因子1(stromal cell derived factor 1, SDF-1)的受体，由 RDC1 基因编码，通过与CXCL11及SDF-1结合发挥其生物学效应。CXCR7在多种肿瘤细胞表面高表达，在肿瘤的发生、发展过程中发挥着重要作用，促进肿瘤细胞的存活和生长、黏附与侵袭、肿瘤血管新生及癌细胞转移。与其他趋化因子受体不同，CXCR7在与SDF-1结合后，并不引起钙离子内流和趋化反应，而是通过建立合适的趋化因子的梯度，与CXCR4 \[chemokine (C-X-C motif) receptor 4\]相互协调发挥作用。以CXCR7为靶点的肿瘤分子治疗研究不断增加，有望为肿瘤治疗提供新的方法。
CXCR7\[chemokine (C-X-C motif) receptor 7\]是一个近年来新发现的基质细胞衍生因子1(stromal cell derived factor 1, SDF-1)的受体，由 RDC1 基因编码，通过与CXCL11及SDF-1结合发挥其生物学效应。CXCR7在多种肿瘤细胞表面高表达，在肿瘤的发生、发展过程中发挥着重要作用，促进肿瘤细胞的存活和生长、黏附与侵袭、肿瘤血管新生及癌细胞转移。与其他趋化因子受体不同，CXCR7在与SDF-1结合后，并不引起钙离子内流和趋化反应，而是通过建立合适的趋化因子的梯度，与CXCR4 \[chemokine (C-X-C motif) receptor 4\]相互协调发挥作用。以CXCR7为靶点的肿瘤分子治疗研究不断增加，有望为肿瘤治疗提供新的方法。
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- 《中国肿瘤生物治疗杂志》
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Supported by:Beijing E-Tiller Technology Development Co., Ltd.