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Volume 25,Issue 6,2018 Table of Contents
2018, 25(6):549-554.
DOI: 10.3872/j.issn.1007-385X.2018.06.001
Abstract:
[Abstract] Cell therapy includes stem cell therapy and immunotherapy for multiple diseases including cancer. With the progress in life science and medicine as well as people’s increasing demands for health, cell therapy has become an important frontier research field.Constantly emerged innovative theories, technologies and clinical outcomes of cell therapy have laid a solid foundation for the development of cell therapy industrialization. Now some cell therapy products have already been approved by the regulatory authorities abroad;and in China, cell therapy is in a period of great opportunities. Therefore, how to optimize the supervision and guiding system and provisions,to better stimulate the vitality of research and transformation, to create more benefits for patients and to promote the development of the industry in an orderly manner have become an issues that worth deep consideration. In this paper, we discussed the current progress on stem cell therapy and immunotherapy represented by chimeric antigen receptor T-Cell (CAR-T) in both domestic and overseas,and the industry supervision of cell therapy in China; in addition, we also put forward some suggestions for the development of cell therapy in China for the reference of peers in this field.
[Abstract] Cell therapy includes stem cell therapy and immunotherapy for multiple diseases including cancer. With the progress in life science and medicine as well as people’s increasing demands for health, cell therapy has become an important frontier research field.Constantly emerged innovative theories, technologies and clinical outcomes of cell therapy have laid a solid foundation for the development of cell therapy industrialization. Now some cell therapy products have already been approved by the regulatory authorities abroad;and in China, cell therapy is in a period of great opportunities. Therefore, how to optimize the supervision and guiding system and provisions,to better stimulate the vitality of research and transformation, to create more benefits for patients and to promote the development of the industry in an orderly manner have become an issues that worth deep consideration. In this paper, we discussed the current progress on stem cell therapy and immunotherapy represented by chimeric antigen receptor T-Cell (CAR-T) in both domestic and overseas,and the industry supervision of cell therapy in China; in addition, we also put forward some suggestions for the development of cell therapy in China for the reference of peers in this field.
2018, 25(6):555-561.
DOI: 10.3872/j.issn.1007-385X.2018.06.002
Abstract:
[Abstract] Objective: To investigate the effect and underlying mechanism of Long non-coding RNA urothelial carcinoma associated 1 (lncRNA UCA1) on proliferation, invasion and migration of non-small cell lung cancer (NSCLC) A549 cells. Methods: NSCLS A549 cells were cultured and transfected with lentivirus; RT-PCR was employed to detect the levels of UCA1 in A549 cells. The relationship between UCA1 and miR-185-5p was validated by luciferase reporter assays. Cell viability of A549 cells was measured by MTT. Cell invasion and migration were determined by Transwell and Wound healing assay, respectively; and western blotting was performed for measuring the levels of Wnt1/β-catenin pathway-related proteins. Results: sh-UCA1 significantly decreased UCA1 expression and increased miR-185-5p expression in A549 cells (all P<0.05). miR-185 inhibitor attenuated the promotion effect of sh-UCA1 on miR-185-5p (P<0.05). UCA1 could significantly down-regulate miR-185-5p expression in A549 cells (P<0.05), which was reversed by miR-185 mimic (P<0.05). Luciferase reporter assay validated the binding site on UCA1 to link miR-185-5p. sh-UCA1 significantly inhibited cell proliferation, invasion and migration of A549 cells (all P<0.05), and also decreased the protein levels of Wnt1, β-catenin and TCF-4 notably (all P<0.05); however, miR-185 inhibitor attenuated such inhibitory effects of sh-UCA1 (P<0.05). Conclusion: UCA1 could promote proliferation, invasion and migration of A549 cells through targeting miR-185-5p, and the mechanisms might be related with activation of Wnt1/β-catenin pathway.
[Abstract] Objective: To investigate the effect and underlying mechanism of Long non-coding RNA urothelial carcinoma associated 1 (lncRNA UCA1) on proliferation, invasion and migration of non-small cell lung cancer (NSCLC) A549 cells. Methods: NSCLS A549 cells were cultured and transfected with lentivirus; RT-PCR was employed to detect the levels of UCA1 in A549 cells. The relationship between UCA1 and miR-185-5p was validated by luciferase reporter assays. Cell viability of A549 cells was measured by MTT. Cell invasion and migration were determined by Transwell and Wound healing assay, respectively; and western blotting was performed for measuring the levels of Wnt1/β-catenin pathway-related proteins. Results: sh-UCA1 significantly decreased UCA1 expression and increased miR-185-5p expression in A549 cells (all P<0.05). miR-185 inhibitor attenuated the promotion effect of sh-UCA1 on miR-185-5p (P<0.05). UCA1 could significantly down-regulate miR-185-5p expression in A549 cells (P<0.05), which was reversed by miR-185 mimic (P<0.05). Luciferase reporter assay validated the binding site on UCA1 to link miR-185-5p. sh-UCA1 significantly inhibited cell proliferation, invasion and migration of A549 cells (all P<0.05), and also decreased the protein levels of Wnt1, β-catenin and TCF-4 notably (all P<0.05); however, miR-185 inhibitor attenuated such inhibitory effects of sh-UCA1 (P<0.05). Conclusion: UCA1 could promote proliferation, invasion and migration of A549 cells through targeting miR-185-5p, and the mechanisms might be related with activation of Wnt1/β-catenin pathway.
2018, 25(6):562-567.
DOI: 10.3872/j.issn.1007-385X.2018.06.003
Abstract:
[Abstract] Objective：To investigate the effect of long-chain non-coding RNA TTTY10 (lncRNA TTTY10) on the migration and invasion of cervical cancer cells, and to explore its regulatory effect on miR-490-3p and HMGB1 (high mobility group box 1) signaling pathways.Methods: Fourteen paris of cervical cancer tissues and corresponding paracancerous tissues resected at the Department of Obstetrics and Gynecology, Affiliated Wuhan Central Hospital of Tongji Medical College from August 2013 to December 2014 were collected for this study. The expression of TTTY10 in cervical cancer tissue and different cervical cancer cell lines were detected by qPCR. Plasmids encoding TTTY10-siRNA or empty plasmids were transfected into cervical cancer CasKicells, and the transfection efficiency was detected by qPCR. Transwell migration assay and Transwell invasion assay were used to detect the migration and invasion abilities of cervical cancer cells after TTTY10 silencing. qPCR was used to detect the expression of miR-490-3p and HMGB1 mRNA after TTTY10 silencing. Dual luciferase reporter assay validated the interaction between miR-490-3p and HMGB1. Western blotting was used to detect the expression of HMGB1 signaling pathway related proteins after TTTY10 silencing. Results: The expression of TTTY10 in cervical cancer tissues was significantly higher than that in paracancerous tissues (P<0.01), the expression of TTTY10 in cervical cancer cell lines was significantly higher than that in cervical epithelial cells (P<0.01). TTTY10-siRNA plasmids could efficiently transfect CasKicells to knockdown TTTY10 expression (P<0.01). Silencing of TTTY10 inhibited the migration and invasion of cervical cancer CasKi cells (P<0.05), promoted the expression of miR-490-3p (P<0.01) and inhibited the expression of HMGB1 mRNA in cervical cancer (P<0.05 or P<0.01). miR-490-3p could specifically bind to the 3'-UTR of HMGB1 mRNA (P<0.01). HMGB1 signaling pathway related proteins were down-regulated after TTTY10 silencing. Conclusion: TTTY10 can target regulate the expression of miR-490-3p and affect the migration and invasion ability of cervical cancer CasKi cells through the HMGB1 signaling pathway; TTTY10 can be used as a diagnostic marker and potential treatment target of cervical cancer.
[Abstract] Objective：To investigate the effect of long-chain non-coding RNA TTTY10 (lncRNA TTTY10) on the migration and invasion of cervical cancer cells, and to explore its regulatory effect on miR-490-3p and HMGB1 (high mobility group box 1) signaling pathways.Methods: Fourteen paris of cervical cancer tissues and corresponding paracancerous tissues resected at the Department of Obstetrics and Gynecology, Affiliated Wuhan Central Hospital of Tongji Medical College from August 2013 to December 2014 were collected for this study. The expression of TTTY10 in cervical cancer tissue and different cervical cancer cell lines were detected by qPCR. Plasmids encoding TTTY10-siRNA or empty plasmids were transfected into cervical cancer CasKicells, and the transfection efficiency was detected by qPCR. Transwell migration assay and Transwell invasion assay were used to detect the migration and invasion abilities of cervical cancer cells after TTTY10 silencing. qPCR was used to detect the expression of miR-490-3p and HMGB1 mRNA after TTTY10 silencing. Dual luciferase reporter assay validated the interaction between miR-490-3p and HMGB1. Western blotting was used to detect the expression of HMGB1 signaling pathway related proteins after TTTY10 silencing. Results: The expression of TTTY10 in cervical cancer tissues was significantly higher than that in paracancerous tissues (P<0.01), the expression of TTTY10 in cervical cancer cell lines was significantly higher than that in cervical epithelial cells (P<0.01). TTTY10-siRNA plasmids could efficiently transfect CasKicells to knockdown TTTY10 expression (P<0.01). Silencing of TTTY10 inhibited the migration and invasion of cervical cancer CasKi cells (P<0.05), promoted the expression of miR-490-3p (P<0.01) and inhibited the expression of HMGB1 mRNA in cervical cancer (P<0.05 or P<0.01). miR-490-3p could specifically bind to the 3'-UTR of HMGB1 mRNA (P<0.01). HMGB1 signaling pathway related proteins were down-regulated after TTTY10 silencing. Conclusion: TTTY10 can target regulate the expression of miR-490-3p and affect the migration and invasion ability of cervical cancer CasKi cells through the HMGB1 signaling pathway; TTTY10 can be used as a diagnostic marker and potential treatment target of cervical cancer.
4 Effect of shRNA interfering BAMBI on malignant biological behaviors of human colon cancer SW480 cell
2018, 25(6):567-573.
DOI: 10.3872/j.issn.1007-385X.2018.06.004
Abstract:
[Abstract] Objective: To explore the effect of shRNA interfering BAMBI (bone morphogenetic protein and activin membrane bound inhibitor) on the proliferation, apoptosis, invasion and migration of human colon cancer SW480 cells and the possible mechanisms.Methods: After successful transfection with sh-BAMBI in SW480 cells, the mRNA and protein epxressions of BAMBI were detected by qRT-PCR and Western blotting, respectively. Cell proliferation was measured by MTT; apoptosis was tested by Hoechst33258 staining;cell invasion was detected by transwell assay; and cell migration was measured by wound healing assay. The expressions of TGF-β/Smad/2 signaling pathway related proteins were detected by Western blotting. Results: The mRNA and protein levels of BAMBI in sh-BAMBI group were lower than those of control group (P<0.05). Compared with control group, cell proliferation in sh-BAMBI group was obviously decreased (P<0.05), while apoptosis was obviously increased (P<0.01); in the meanwhile, cell invasion and migration in sh-BAMBI group were significantly reduced (P<0.05). In addition, the protein level of TGF-β and the ratio of p-Smad/2/ Smad/2 in sh-BAMBI group were significantly higher than those in control group (P<0.05). Conclusion: Interference of BAMBI by shRNA inhibits proliferation, invasion and migration but induces apoptosis of human colon cancer SW480 cells and activates TGF-β/Smad/2 pathway.
[Abstract] Objective: To explore the effect of shRNA interfering BAMBI (bone morphogenetic protein and activin membrane bound inhibitor) on the proliferation, apoptosis, invasion and migration of human colon cancer SW480 cells and the possible mechanisms.Methods: After successful transfection with sh-BAMBI in SW480 cells, the mRNA and protein epxressions of BAMBI were detected by qRT-PCR and Western blotting, respectively. Cell proliferation was measured by MTT; apoptosis was tested by Hoechst33258 staining;cell invasion was detected by transwell assay; and cell migration was measured by wound healing assay. The expressions of TGF-β/Smad/2 signaling pathway related proteins were detected by Western blotting. Results: The mRNA and protein levels of BAMBI in sh-BAMBI group were lower than those of control group (P<0.05). Compared with control group, cell proliferation in sh-BAMBI group was obviously decreased (P<0.05), while apoptosis was obviously increased (P<0.01); in the meanwhile, cell invasion and migration in sh-BAMBI group were significantly reduced (P<0.05). In addition, the protein level of TGF-β and the ratio of p-Smad/2/ Smad/2 in sh-BAMBI group were significantly higher than those in control group (P<0.05). Conclusion: Interference of BAMBI by shRNA inhibits proliferation, invasion and migration but induces apoptosis of human colon cancer SW480 cells and activates TGF-β/Smad/2 pathway.
RAN Lijinga，
,
ZENG Yuna
,
WANG Shaochun
,
ZHANG Disia
,
YI Xiangweia，
,
HONG Minb
,
LI Shaoyoub
,
DONG Jianb
,
DU Mingyuc
,
SHI Mingxia
2018, 25(6):574-581.
DOI: 10.3872/j.issn.1007-385X.2018.06.005
Abstract:
[Abstract] Objective: The aim of this study was to investigate the effect of co-culture with AEC (amniotic epithelial cell) on the biological characteristics of AMSC (amniotic mesenchymal stem cell), and to investigate the roles of SDF-1/CXCR4 axis in the homing and migration of AMSC. Methods: AMSC and AEC were isolated from human amnion, and then cultured, amplified and identified, respectively.The AMSC were divided into three groups: AEC co-cultured group, serum-free cultured group and serum cultured group. After culture for 24 h, 48 h, and 72 h, the proliferation viability of AMSC was measured by CCK-8 assay and trypan blue staining; the expression of CXCR4 mRNA was analyzed by flow cytometry and Real-time RT-PCR, and the migration ability of AMSC in vitro was observed by migration assay. Results: Cell viability (48 h and 72 h) and survival rate in the co-culture and serum groups were higher than those in the serum-free group (all P<0.05). The mRNA and protein expressions of CXCR4 in AMSC of the co-culture and serum-free groups were significantly higher than those of the serum group (P<0.05). The migration ability of AMSC in the co-culture and serumfree groups, which increase with the SDF-1 (stromal cell derived factor-1) concentration gradient, were higher than that in the serum group (P<0.05). Conclusion: AMSC co-cultured with AEC still have the basic biological characteristics of MSC, and showed good growth activity. Co-culture with AEC can up-regulate CXCR4 on AMSC surfaces and enhance the migration ability of AMSC in vitro.
[Abstract] Objective: The aim of this study was to investigate the effect of co-culture with AEC (amniotic epithelial cell) on the biological characteristics of AMSC (amniotic mesenchymal stem cell), and to investigate the roles of SDF-1/CXCR4 axis in the homing and migration of AMSC. Methods: AMSC and AEC were isolated from human amnion, and then cultured, amplified and identified, respectively.The AMSC were divided into three groups: AEC co-cultured group, serum-free cultured group and serum cultured group. After culture for 24 h, 48 h, and 72 h, the proliferation viability of AMSC was measured by CCK-8 assay and trypan blue staining; the expression of CXCR4 mRNA was analyzed by flow cytometry and Real-time RT-PCR, and the migration ability of AMSC in vitro was observed by migration assay. Results: Cell viability (48 h and 72 h) and survival rate in the co-culture and serum groups were higher than those in the serum-free group (all P<0.05). The mRNA and protein expressions of CXCR4 in AMSC of the co-culture and serum-free groups were significantly higher than those of the serum group (P<0.05). The migration ability of AMSC in the co-culture and serumfree groups, which increase with the SDF-1 (stromal cell derived factor-1) concentration gradient, were higher than that in the serum group (P<0.05). Conclusion: AMSC co-cultured with AEC still have the basic biological characteristics of MSC, and showed good growth activity. Co-culture with AEC can up-regulate CXCR4 on AMSC surfaces and enhance the migration ability of AMSC in vitro.
2018, 25(6):582-589.
DOI: 10.3872/j.issn.1007-385X.2018.06.006
Abstract:
[Abstract] Objective: To prepare the fusion protein mGM-CSF-GnRH3 (mGGn) of mouse granulocyte-macrophage colony stimulating factor (mGM-CSF) combining with gonadotropin releasing hormone (GnRH) and the fusion protein mGM-CSF-GRP6 (mG6) of mGM-CSF combining with gastrin-releasing peptide (GRP), and to investigate the inhibitory effect of the above two fusion proteins on B16F10 melanoma in vitro as well as to preliminarily predict their isoelectric point, relative molecular weight,hydrophobicity,stability,subcellular localization, signal peptide, spatial structure and potential epitopes. Methods: After the successful preparation of mGGn and mG6, the effects of different concentrations of fusion proteins on tumor cell morphology, migration, proliferation and cell cycle were detected by microscopic observation, scratch test, CCK-8 method and flow cytometry, respectively. The protein online analysis systems EXPASY, GOR4, SWISS MODEL were used to predict the basic properties and secondary/tertiary structure of recombinant fusion proteins.The B cell epitopes were predicted by IEDB and ABCpred software, the CTL epitopes were comprehensively predicted by SYFPEITHI,BlMAS and NetCTL software, and the Th epitopes were predicted by NetMHCIIpan 3.1 Server and IEDB software. Results:Both mGGn and mG6 inhibited the migration and proliferation of tumor cells. mGGn could block B16F10 cell cycle at G1 phase while mG6 could block B16F10 cell cycle at S phase, all of which prevented cells entering into G2 phase to inhibit tumor cell growth. The mGGn and mG6 fusion proteins got diverse structures and had multiple potential B epitopes, CTL epitopes and Th epitopes.Conclusion:mGGn and mG6 have inhibitory effect on B16F10 melanoma in vitro, and bioinformatics predictions have laid a foundation for further study of the biological functions and immunological activities of these fusion proteins.
[Abstract] Objective: To prepare the fusion protein mGM-CSF-GnRH3 (mGGn) of mouse granulocyte-macrophage colony stimulating factor (mGM-CSF) combining with gonadotropin releasing hormone (GnRH) and the fusion protein mGM-CSF-GRP6 (mG6) of mGM-CSF combining with gastrin-releasing peptide (GRP), and to investigate the inhibitory effect of the above two fusion proteins on B16F10 melanoma in vitro as well as to preliminarily predict their isoelectric point, relative molecular weight,hydrophobicity,stability,subcellular localization, signal peptide, spatial structure and potential epitopes. Methods: After the successful preparation of mGGn and mG6, the effects of different concentrations of fusion proteins on tumor cell morphology, migration, proliferation and cell cycle were detected by microscopic observation, scratch test, CCK-8 method and flow cytometry, respectively. The protein online analysis systems EXPASY, GOR4, SWISS MODEL were used to predict the basic properties and secondary/tertiary structure of recombinant fusion proteins.The B cell epitopes were predicted by IEDB and ABCpred software, the CTL epitopes were comprehensively predicted by SYFPEITHI,BlMAS and NetCTL software, and the Th epitopes were predicted by NetMHCIIpan 3.1 Server and IEDB software. Results:Both mGGn and mG6 inhibited the migration and proliferation of tumor cells. mGGn could block B16F10 cell cycle at G1 phase while mG6 could block B16F10 cell cycle at S phase, all of which prevented cells entering into G2 phase to inhibit tumor cell growth. The mGGn and mG6 fusion proteins got diverse structures and had multiple potential B epitopes, CTL epitopes and Th epitopes.Conclusion:mGGn and mG6 have inhibitory effect on B16F10 melanoma in vitro, and bioinformatics predictions have laid a foundation for further study of the biological functions and immunological activities of these fusion proteins.
2018, 25(6):590-594.
DOI: 10.3872/j.issn.1007-385X.2018.06.007
Abstract:
[Abstract] Objective: To investigate Ginsenoside Rg3 interfering the expression of CaM through PI3K/AKT signaling pathway to affect the biological activity of gastric cancer BGC-823 cells. Methods: After the culture and passage of gastric cancer BGC-823 cells,Western blotting was used to detect the expression of p-AKT and CaM protein in gastric cancer BGC-823 cells treated with IGF-1 and/or Rg3; The effect of IGF-1 and/or Rg3 on the proliferation of BGC-823 cells was detected by MTT assay; The effect of IGF-1 and/or Rg3 on the invasion of BGC-823 cells was detected by Transwell assay; Effect of IGF-1 and/or Rg3 on apoptosis of BGC-823 cells was detected by Flow Cytometry. Results: Western blotting results showed that the expression of p-AKT and CaM protein increased in BGC-823 cells with the prolongation of IGF-1 treatment (all P<0.05); Compared with the blank control group, Rg3 significantly inhibited the proliferation of BGC-823 cells, while IGF-1 and IGF-1+Rg3 significantly promoted the cell proliferation (all P<0.05); Compared with the blank control group, Rg3 significantly reduced the invasion of BGC-823 cells, while IGF-1 and IGF-1+Rg3 significantly promoted the invasion of BGC-823 cells (all P<0.05);Flow cytometry showed that compared with the blank control group, Rg3 significantly promoted the apoptosis of BGC-823 cells, while IGF-1 and IGF-1+Rg3 significantly inhibited the apoptosis of BGC-823 cells (all P<0.05). Conclusion: Ginsenoside Rg3 inhibits the expression of CaM by blocking PI3K/AKT signaling pathway, thereby promoting the apoptosis of gastric cancer BGC-823 cells.
[Abstract] Objective: To investigate Ginsenoside Rg3 interfering the expression of CaM through PI3K/AKT signaling pathway to affect the biological activity of gastric cancer BGC-823 cells. Methods: After the culture and passage of gastric cancer BGC-823 cells,Western blotting was used to detect the expression of p-AKT and CaM protein in gastric cancer BGC-823 cells treated with IGF-1 and/or Rg3; The effect of IGF-1 and/or Rg3 on the proliferation of BGC-823 cells was detected by MTT assay; The effect of IGF-1 and/or Rg3 on the invasion of BGC-823 cells was detected by Transwell assay; Effect of IGF-1 and/or Rg3 on apoptosis of BGC-823 cells was detected by Flow Cytometry. Results: Western blotting results showed that the expression of p-AKT and CaM protein increased in BGC-823 cells with the prolongation of IGF-1 treatment (all P<0.05); Compared with the blank control group, Rg3 significantly inhibited the proliferation of BGC-823 cells, while IGF-1 and IGF-1+Rg3 significantly promoted the cell proliferation (all P<0.05); Compared with the blank control group, Rg3 significantly reduced the invasion of BGC-823 cells, while IGF-1 and IGF-1+Rg3 significantly promoted the invasion of BGC-823 cells (all P<0.05);Flow cytometry showed that compared with the blank control group, Rg3 significantly promoted the apoptosis of BGC-823 cells, while IGF-1 and IGF-1+Rg3 significantly inhibited the apoptosis of BGC-823 cells (all P<0.05). Conclusion: Ginsenoside Rg3 inhibits the expression of CaM by blocking PI3K/AKT signaling pathway, thereby promoting the apoptosis of gastric cancer BGC-823 cells.
2018, 25(6):595-600.
DOI: 10.3872/j.issn.1007-385X.2018.06.008
Abstract:
[Abstract] Objective: To explore the resistance of CD133+ cells in HepG2 cell line to doxorubicin (DOX) and its mechanism. Methods:CD133+ cells were sorted by magnetic beads and CD133+ positive rate was detected by flow cytometry. MTT assay was used to detect the resistance to DOX-induced apoptosis of CD133+ cells. The expression of BCRP transporter mRNA was detected by RT-PCR.The expression of apoptosis-related proteins was detected by Western blotting. Immunofluorescence assay was used to detect the activation and transportation of P65 after DOX treatment. Results: Magnetic beads sorting could efficiently sort the CD133+ cells from HepG2 cells. MTT proliferation assay showed that CD133+ cells had stronger resistance to DOX than CD133- cells (P<0.05). Immunofluorescence showed that the activation rate and content of P65 in CD133+ cells were significantly higher than those in CD133- cells and HepG2 cells (P<0.05). The results of RT-PCR showed that the mRNA content of BCRP in CD133+ cells was significantly increased compared with CD133- cells and HepG2 cells (all P<0.05). Compared with HepG2 and CD133- groups, the expression of Bax and p53 in CD133+ cells was significantly decreased (P<0.05), while the expression of Bcl-2 and Survivin protein in CD133+ cells was significantly increased (P<0.05 or P<0.01). Conclusion: The molecular mechanism of high DOX-resistance of the CD133+ cell subsets in HepG2 cells is the high expression of the survival-related proteins NF-κB, Bcl-2, Survivin and the drug-resistance transporter BCRP,and low expression of apoptosis-promoting proteins p53 and Bax.
[Abstract] Objective: To explore the resistance of CD133+ cells in HepG2 cell line to doxorubicin (DOX) and its mechanism. Methods:CD133+ cells were sorted by magnetic beads and CD133+ positive rate was detected by flow cytometry. MTT assay was used to detect the resistance to DOX-induced apoptosis of CD133+ cells. The expression of BCRP transporter mRNA was detected by RT-PCR.The expression of apoptosis-related proteins was detected by Western blotting. Immunofluorescence assay was used to detect the activation and transportation of P65 after DOX treatment. Results: Magnetic beads sorting could efficiently sort the CD133+ cells from HepG2 cells. MTT proliferation assay showed that CD133+ cells had stronger resistance to DOX than CD133- cells (P<0.05). Immunofluorescence showed that the activation rate and content of P65 in CD133+ cells were significantly higher than those in CD133- cells and HepG2 cells (P<0.05). The results of RT-PCR showed that the mRNA content of BCRP in CD133+ cells was significantly increased compared with CD133- cells and HepG2 cells (all P<0.05). Compared with HepG2 and CD133- groups, the expression of Bax and p53 in CD133+ cells was significantly decreased (P<0.05), while the expression of Bcl-2 and Survivin protein in CD133+ cells was significantly increased (P<0.05 or P<0.01). Conclusion: The molecular mechanism of high DOX-resistance of the CD133+ cell subsets in HepG2 cells is the high expression of the survival-related proteins NF-κB, Bcl-2, Survivin and the drug-resistance transporter BCRP,and low expression of apoptosis-promoting proteins p53 and Bax.
9 Licorice enhances radio-sensitivity of nasopharyngeal carcinoma CNE-2 cells by affecting autophagy
2018, 25(6):601-606.
DOI: 10.3872/j.issn.1007-385X.2018.06.009
Abstract:
[Abstract] Objective: To investigate the effect of licorice on radio-sensitization of nasopharyngeal carcinoma CNE-2 cells and its mechanism. Methods: The radio-resistant nasopharyngeal carcinoma cell line (CNE-2-RR) was constructed and cultured in vitro. MTT assay was used to detect the effect of different concentrations of licorice on the proliferation activity of nasopharyngeal carcinoma cells.The changes of autophagosome in CNE-2-RR cells after licorice treatment were observed by transmission electron microscopy (TEM).Western blotting was used to detect the effect of licorice on the level of autophagy protein in CNE-2-RR cells. Single cell gel electrophoresis (comet assay) was used to detect the DNA damage and repair of different groups of CNE-2-RR cells. Flow cytometry was used to detect the apoptosis rate of CNE-2-RR cell line. Results: Low-radiation resistant CNE-2-RR cell line was successfully constructed;MTT assay showed that 20 mmol/L licorice exhibited highest inhibition on CNE-2-RR cells (58.86 ± 5.02)%. Transmission electron microscopy showed increased autophagicbody and abnormal mitochondria and nuclei morphology in CNE-2-RR cells after treatment.Western blotting showed that autophagic protein LC3-II level was increased and LC3-I level was decreased in CNE-2-RR cells (P <0.05). The results of single cell gel electrophoresis showed that the length of comet tail distance of CNE-2-RR cells after licorice treatment was higher than that of the control group (P<0.05), indicating weakened repair ability of DNA damage. Conclusion: Licorice enhances the radio-sensitivity of CNE-2-RR cells by influencing autophagy and DNA repair ability.
[Abstract] Objective: To investigate the effect of licorice on radio-sensitization of nasopharyngeal carcinoma CNE-2 cells and its mechanism. Methods: The radio-resistant nasopharyngeal carcinoma cell line (CNE-2-RR) was constructed and cultured in vitro. MTT assay was used to detect the effect of different concentrations of licorice on the proliferation activity of nasopharyngeal carcinoma cells.The changes of autophagosome in CNE-2-RR cells after licorice treatment were observed by transmission electron microscopy (TEM).Western blotting was used to detect the effect of licorice on the level of autophagy protein in CNE-2-RR cells. Single cell gel electrophoresis (comet assay) was used to detect the DNA damage and repair of different groups of CNE-2-RR cells. Flow cytometry was used to detect the apoptosis rate of CNE-2-RR cell line. Results: Low-radiation resistant CNE-2-RR cell line was successfully constructed;MTT assay showed that 20 mmol/L licorice exhibited highest inhibition on CNE-2-RR cells (58.86 ± 5.02)%. Transmission electron microscopy showed increased autophagicbody and abnormal mitochondria and nuclei morphology in CNE-2-RR cells after treatment.Western blotting showed that autophagic protein LC3-II level was increased and LC3-I level was decreased in CNE-2-RR cells (P <0.05). The results of single cell gel electrophoresis showed that the length of comet tail distance of CNE-2-RR cells after licorice treatment was higher than that of the control group (P<0.05), indicating weakened repair ability of DNA damage. Conclusion: Licorice enhances the radio-sensitivity of CNE-2-RR cells by influencing autophagy and DNA repair ability.
2018, 25(6):607-612.
DOI: 10.3872/j.issn.1007-385X.2018.06.010
Abstract:
[Abstract] Objective: To investigate the expression profile and function of FANCF gene (a key gene in FA/BRCA pathway) in both cisplatin (DDP)-resistant and DDP-sensitive human triple-negative breast cancer cell lines and to analyze its correlation with DDP-resistance in breast cancer. Methods: The DDP-resistant breast cancer MDA-MB-231 cell line (MDA-MB-231/DDP) was established by induction of gradient DDP. The expression of FANCF gene in both sensitive and resistant cell lines was knocked-down by RNAi interference technology and the knockdown efficiency was validated at both RNA and protein level. The cell viability of MDA-MB-231 cells and MDA-MB-231/DDP cells was determined by the CCK8 assay; Flow cytometry was used to examine the cell cycle distribution and apoptosis; the mRNA and protein expressions of FANCF gene were examined by using qRT-PCR and western blotting, respectively. Results:The resistance index of MDA-MB-231 /DDP cells was 13.5 after 3-month induction. The mRNA and protein expressions of FANCF were significantly increased in MDA-MB-231/DDP cells (all P<0.01). Cell cycle analysis indicated that the DDP treatment significantly induced G0/G1 arrest and decreased the cell proportion in phase S and G2/M. siRNA-mediated knockdown of FANCF could not only be able to increase sensitivity of MDA-MB-231 to DDP but also promote the cell apoptosis (all P<0.01). Conclusion: FANCF attributes to the occurrence of DDP-resistance through anti-apoptosis effect, which might be served as a potential treatment target for drug-resistant human breast cancer.
[Abstract] Objective: To investigate the expression profile and function of FANCF gene (a key gene in FA/BRCA pathway) in both cisplatin (DDP)-resistant and DDP-sensitive human triple-negative breast cancer cell lines and to analyze its correlation with DDP-resistance in breast cancer. Methods: The DDP-resistant breast cancer MDA-MB-231 cell line (MDA-MB-231/DDP) was established by induction of gradient DDP. The expression of FANCF gene in both sensitive and resistant cell lines was knocked-down by RNAi interference technology and the knockdown efficiency was validated at both RNA and protein level. The cell viability of MDA-MB-231 cells and MDA-MB-231/DDP cells was determined by the CCK8 assay; Flow cytometry was used to examine the cell cycle distribution and apoptosis; the mRNA and protein expressions of FANCF gene were examined by using qRT-PCR and western blotting, respectively. Results:The resistance index of MDA-MB-231 /DDP cells was 13.5 after 3-month induction. The mRNA and protein expressions of FANCF were significantly increased in MDA-MB-231/DDP cells (all P<0.01). Cell cycle analysis indicated that the DDP treatment significantly induced G0/G1 arrest and decreased the cell proportion in phase S and G2/M. siRNA-mediated knockdown of FANCF could not only be able to increase sensitivity of MDA-MB-231 to DDP but also promote the cell apoptosis (all P<0.01). Conclusion: FANCF attributes to the occurrence of DDP-resistance through anti-apoptosis effect, which might be served as a potential treatment target for drug-resistant human breast cancer.
ZHOU Xinlianga
,
WU Haob
,
LI Dana
,
WANG Feifeic
,
CUI Yanzhia
,
ZHAO Lianmeib
,
SANG Meixiangb
,
SHAN Baoenb
,
2018, 25(6):613-619.
DOI: 10.3872/j.issn.1007-385X.2018.06.011
Abstract:
[Abstract] Objective: To detect the expression of miR-133a-3p in gastric cancer (GC) tissues and plasma of GC patients, and to investigate its effect on the proliferation of GC cells as well as its correlation toprognosis of GC patients. Methods: 52 cases of cancertissues (non-necrosis part) and corresponding adjacent tissues as well as the pre-operative peripheral blood samples from GC patients, who underwent surgery at Department of General Surgery, the Forth Hospital of Hebei Medical University(Shijiazhuang, China) between May 2012 and May 2013, were collected for this study. The plasma sample (n=35) from healthy donors were obtained during their physical examination. RT-qPCR was adopted to detect the expression of miR-133a-3p in gastric cancer tissues, adjacent tissuesand plasma samples of GC patients and healthy volunteers. The relationships between miR-133a-3p expression and the median DFS as well as clinicopathological parameters were also analyzed. CCK-8 assay was adopted to detect the effect of miR-133a-3p silence or over-expression on proliferation of gastric cancer SGC7901 cells. Results: miR-133a-3p was dramatically decreased in gastric cancer tissues (P<0.01),and its expression was associated with TNM stage, tumor infiltration (T), lynphonode metastasis (N), and vascular tumor thrombus (all P<0.01); miR-133a-3p was significantly increased in the plasma of GC patients (P<0.01), and its expression was associated with TNM stage, lynphonode metastasis (N), and vascular tumor thrombus (all P<0.05). miR-133a-3p expression was positively correlated with serum CA199 level of GC patients (P<0.01). The median DFS of patients with high miR-133a-3pexpression in cancer tissues was significantly longer than that of the patients with low expression(20.8 vs 14.8 months, P<0.05); The median DFS of patients with high plasma miR-133a-3p expression was significantly shorter than that of the patients with low expression (14.4 vs 20.3 months, P<0.05). Over-expression of miR-133a-3p could significantly inhibit the proliferation of gastric cancer SGC7901 cells, while miR-133a-3p silence could significantly promote the proliferation (all P<0.05). Conclusion: miR-133a-3p could significantlyinhibit the proliferation of SGC7901 cells; miR-133a-3p aberrantlyexpressed in gastric cancer tissues and plasma, and obviously correlated with prognosis of gastric cancer patients, which may be used as a potential clinical bio-maker for early diagnosis and treatment as well as the prognosis prediction of gastric cancer.
[Abstract] Objective: To detect the expression of miR-133a-3p in gastric cancer (GC) tissues and plasma of GC patients, and to investigate its effect on the proliferation of GC cells as well as its correlation toprognosis of GC patients. Methods: 52 cases of cancertissues (non-necrosis part) and corresponding adjacent tissues as well as the pre-operative peripheral blood samples from GC patients, who underwent surgery at Department of General Surgery, the Forth Hospital of Hebei Medical University(Shijiazhuang, China) between May 2012 and May 2013, were collected for this study. The plasma sample (n=35) from healthy donors were obtained during their physical examination. RT-qPCR was adopted to detect the expression of miR-133a-3p in gastric cancer tissues, adjacent tissuesand plasma samples of GC patients and healthy volunteers. The relationships between miR-133a-3p expression and the median DFS as well as clinicopathological parameters were also analyzed. CCK-8 assay was adopted to detect the effect of miR-133a-3p silence or over-expression on proliferation of gastric cancer SGC7901 cells. Results: miR-133a-3p was dramatically decreased in gastric cancer tissues (P<0.01),and its expression was associated with TNM stage, tumor infiltration (T), lynphonode metastasis (N), and vascular tumor thrombus (all P<0.01); miR-133a-3p was significantly increased in the plasma of GC patients (P<0.01), and its expression was associated with TNM stage, lynphonode metastasis (N), and vascular tumor thrombus (all P<0.05). miR-133a-3p expression was positively correlated with serum CA199 level of GC patients (P<0.01). The median DFS of patients with high miR-133a-3pexpression in cancer tissues was significantly longer than that of the patients with low expression(20.8 vs 14.8 months, P<0.05); The median DFS of patients with high plasma miR-133a-3p expression was significantly shorter than that of the patients with low expression (14.4 vs 20.3 months, P<0.05). Over-expression of miR-133a-3p could significantly inhibit the proliferation of gastric cancer SGC7901 cells, while miR-133a-3p silence could significantly promote the proliferation (all P<0.05). Conclusion: miR-133a-3p could significantlyinhibit the proliferation of SGC7901 cells; miR-133a-3p aberrantlyexpressed in gastric cancer tissues and plasma, and obviously correlated with prognosis of gastric cancer patients, which may be used as a potential clinical bio-maker for early diagnosis and treatment as well as the prognosis prediction of gastric cancer.
2018, 25(6):620-628.
DOI: 10.3872/j.issn.1007-385X.2018.06.012
Abstract:
[Abstract] Objective: To investigate the relationship between the expression of RUNX1 isoforms and the clinical curative effect and the prognosis of acute leukemia (AL), in order to provide valuable experimental data for the individualized treatment, MRD (minimal residual disease) monitoring and prognosis prediction of AL. Methods: AL patients with primary treatment (PT, n=88) and recrudescence (RC, n=10) that treated at the Department of Hematology of Affiliated Hospital of Guangdong Medical University from April,2012 to April, 2013 were included in this study. Real-time PCR was used to examine the mRNA expression of RUNX1 isoforms (RUNX1a and RUNX1b / c) in PT patients, RC patients and controls (non-malignant hematological disease patients). The changes in mRNA expression of RUNX1a and RUNX1b/c in patients before and after the chemotherapy were also observed. Results：(1)The expression levels of RUNX1a mRNA in AML and ALL PT group and AML RC group was significantly higher than those of control group (P<0.05); The expression level of RUNX1a mRNA in AML PT group was increased compared with ALL PT group (P<0.05). (2) The expression levels of RUNX1a and RUNX1b/c mRNA in AML and ALL patients at initial treatment were significantly higher than those after complete remission (CR) (P<0.05). (3) By comparing the expression levels of RUNX1a and RUNX1b/c mRNA at initial diagnosis,there was no significant difference between 6-month death group and survival group, CR group and NCR (non-complete remission)group after first cycle of chemotherapy, or the high leukocyte group and non-high leukocyte group (all P>0.05).The expression level of RUNX1a mRNA in AML-ETO positive group was higher than that of negative group (P<0.05). (4) The expression levels of RUNX1a and RUNX1b/c mRNA in patients with acute leukemia decreased with the increasing chemotherapy cycle, and significantly increased when had a relapse, which may even succeed the initial level.Conclusion: RUNX1a isoforms participate in the pathogenesis of acute leukemia, and isrelated to the relapse of AML. The expression levels of RUNX1a and RUNX1b/c mRNA are related to the clinical efficacy that can be used as an indicator of curative effect, but have no significant correlation with the prognosis of the disease.Dynamic monitor of theexpression levels of RUNX1a and RUNX1b/c isomers can be used as an effective indicator of MRD monitoring after chemotherapy,which can be used to evaluate the efficacy and identify the risk of recurrence at early stage.
[Abstract] Objective: To investigate the relationship between the expression of RUNX1 isoforms and the clinical curative effect and the prognosis of acute leukemia (AL), in order to provide valuable experimental data for the individualized treatment, MRD (minimal residual disease) monitoring and prognosis prediction of AL. Methods: AL patients with primary treatment (PT, n=88) and recrudescence (RC, n=10) that treated at the Department of Hematology of Affiliated Hospital of Guangdong Medical University from April,2012 to April, 2013 were included in this study. Real-time PCR was used to examine the mRNA expression of RUNX1 isoforms (RUNX1a and RUNX1b / c) in PT patients, RC patients and controls (non-malignant hematological disease patients). The changes in mRNA expression of RUNX1a and RUNX1b/c in patients before and after the chemotherapy were also observed. Results：(1)The expression levels of RUNX1a mRNA in AML and ALL PT group and AML RC group was significantly higher than those of control group (P<0.05); The expression level of RUNX1a mRNA in AML PT group was increased compared with ALL PT group (P<0.05). (2) The expression levels of RUNX1a and RUNX1b/c mRNA in AML and ALL patients at initial treatment were significantly higher than those after complete remission (CR) (P<0.05). (3) By comparing the expression levels of RUNX1a and RUNX1b/c mRNA at initial diagnosis,there was no significant difference between 6-month death group and survival group, CR group and NCR (non-complete remission)group after first cycle of chemotherapy, or the high leukocyte group and non-high leukocyte group (all P>0.05).The expression level of RUNX1a mRNA in AML-ETO positive group was higher than that of negative group (P<0.05). (4) The expression levels of RUNX1a and RUNX1b/c mRNA in patients with acute leukemia decreased with the increasing chemotherapy cycle, and significantly increased when had a relapse, which may even succeed the initial level.Conclusion: RUNX1a isoforms participate in the pathogenesis of acute leukemia, and isrelated to the relapse of AML. The expression levels of RUNX1a and RUNX1b/c mRNA are related to the clinical efficacy that can be used as an indicator of curative effect, but have no significant correlation with the prognosis of the disease.Dynamic monitor of theexpression levels of RUNX1a and RUNX1b/c isomers can be used as an effective indicator of MRD monitoring after chemotherapy,which can be used to evaluate the efficacy and identify the risk of recurrence at early stage.
LI Zhenjia
,
XU SumingΔ
,
CHEN Ruoxi
,
LI Jiaxi
,
YU Fanqi
,
LI Yimin
,
YU Mengqi
,
ZOU Zhenhong
,
LIANG Bo
,
YU Liming
2018, 25(6):629-633.
DOI: 10.3872/j.issn.1007-385X.2018.06.013
Abstract:
[Abstract] Objective: To investigate the expression of Flotillin-2 (Flot-2) protein in gastric cancer tissues and its relationship with clinicopathological features and prognosis of gastric cancer (GC) patients. Methods: 112 samples of gastric cancer tissue and the corresponding paracancerous tissue that resected at the gastrointestinal surgery department of the Second Affiliated Hospital of Nanchang University between January 2009 and April 2010 were collected for this study. The expression of Flot-2 protein in tumor tissues was detected by immunohistochemistry. The survival data were analyzed by Kaplan-Meier and Log-Rank test, and the survival curve was plotted.Spearman correlation analysis was used to examine the relationship between Flot-2 protein expression and clinicopathological characteristics and prognosis of GC patients. Results: In gastric cancer tissues, Flot-2 was primary stained in cytoplasm. Level of Flot-2 was significantly higher in gastric cancer tissues compared with that in paracancerous tissues (53.57% vs 46.43%, P<0.05). Expression of Flot-2 in tumor tissues was significantly associated with tumor size, depth of invasion, lymph node metastasis, distant metastasis and AJCC stage (all P<0.01), but not with gender, age, differentiation degree and tumor location (P>0.05). Moreover, survival analysis showed that the overall survival of patients with low Flot-2 expression was significantly higher than that of the patients with high level (P<0.01). Cox regression analysis indicated that distant metastasis, AJCC stage and Flot-2 expression were the independent risk factors for the prognosis of GC patients. Conclusion: Flot-2 protein was highly expressed in gastric cancer tissues and closely correlated with the poor prognosis of GC patients; Flot-2 is an independent risk factor for GC prognosis and may be served as a potential therapeutic target for gastric cancer.
[Abstract] Objective: To investigate the expression of Flotillin-2 (Flot-2) protein in gastric cancer tissues and its relationship with clinicopathological features and prognosis of gastric cancer (GC) patients. Methods: 112 samples of gastric cancer tissue and the corresponding paracancerous tissue that resected at the gastrointestinal surgery department of the Second Affiliated Hospital of Nanchang University between January 2009 and April 2010 were collected for this study. The expression of Flot-2 protein in tumor tissues was detected by immunohistochemistry. The survival data were analyzed by Kaplan-Meier and Log-Rank test, and the survival curve was plotted.Spearman correlation analysis was used to examine the relationship between Flot-2 protein expression and clinicopathological characteristics and prognosis of GC patients. Results: In gastric cancer tissues, Flot-2 was primary stained in cytoplasm. Level of Flot-2 was significantly higher in gastric cancer tissues compared with that in paracancerous tissues (53.57% vs 46.43%, P<0.05). Expression of Flot-2 in tumor tissues was significantly associated with tumor size, depth of invasion, lymph node metastasis, distant metastasis and AJCC stage (all P<0.01), but not with gender, age, differentiation degree and tumor location (P>0.05). Moreover, survival analysis showed that the overall survival of patients with low Flot-2 expression was significantly higher than that of the patients with high level (P<0.01). Cox regression analysis indicated that distant metastasis, AJCC stage and Flot-2 expression were the independent risk factors for the prognosis of GC patients. Conclusion: Flot-2 protein was highly expressed in gastric cancer tissues and closely correlated with the poor prognosis of GC patients; Flot-2 is an independent risk factor for GC prognosis and may be served as a potential therapeutic target for gastric cancer.
2018, 25(6):634-639.
DOI: 10.3872/j.issn.1007-385X.2018.06.014
Abstract:
[摘要] 对急性髓细胞性白血病（acute myeloid leukemia，AML）的治疗，在过去的40 年除了传统的化疗和异基因造血干细胞移植外尚未有很大的进展。而近些年来，随着分子生物学、免疫学等学科的不断发展，免疫检查点抑制剂、过继性免疫效应细胞治疗、肿瘤疫苗等免疫疗法在治疗AML 上初现锋芒。程序性死亡受体（programmed death-1, PD-1）和程序性死亡配体（programmeddeath-1 ligands, PD-L1）抑制剂是一种免疫检查点抑制剂，是目前最受瞩目的研究热点之一，其在治疗AML方面也取得了一些令人鼓舞的进展。本文综述了PD-1/PD-L1 抑制剂治疗AML的机制，其单药应用以及与其他化疗药物或免疫疗法联合应用的研究进展，并分析了这些治疗方法存在的问题。
[摘要] 对急性髓细胞性白血病（acute myeloid leukemia，AML）的治疗，在过去的40 年除了传统的化疗和异基因造血干细胞移植外尚未有很大的进展。而近些年来，随着分子生物学、免疫学等学科的不断发展，免疫检查点抑制剂、过继性免疫效应细胞治疗、肿瘤疫苗等免疫疗法在治疗AML 上初现锋芒。程序性死亡受体（programmed death-1, PD-1）和程序性死亡配体（programmeddeath-1 ligands, PD-L1）抑制剂是一种免疫检查点抑制剂，是目前最受瞩目的研究热点之一，其在治疗AML方面也取得了一些令人鼓舞的进展。本文综述了PD-1/PD-L1 抑制剂治疗AML的机制，其单药应用以及与其他化疗药物或免疫疗法联合应用的研究进展，并分析了这些治疗方法存在的问题。
15 Research progress of bone destruction related signaling pathways in bone metastases from lung cancer
2018, 25(6):640-644.
DOI: 10.3872/j.issn.1007-385X.2018.06.015
Abstract:
[摘要] 晚期肺癌患者骨转移发病率高，骨折、神经压迫、骨痛等并发症多，不仅影响患者的生活质量，而且增加了患者的经济负担及心理压力。肺癌骨转移后，癌细胞和骨组织微环境间进行复杂的相互作用，有多种相关信号通路参与其中，通过复杂的机制最终形成成骨性骨破坏、溶骨性骨破坏及混合性骨破坏。尽管目前对相关信号通路的研究取得了一定的成果，但其在调控成骨/破骨细胞分化及骨形成/骨溶解方面的确切分子机制及相互作用方式仍未阐明。随着研究的进一步深入，将会揭开肺癌骨转移后骨破坏过程的完整机制，为临床有效防治肺癌骨转移提供新的理论依据与治疗靶点。本文从溶骨性骨破坏、成骨性骨破坏和混合性骨破坏3个方面阐述近年来对肺癌骨转移后骨破坏相关信号通路的研究进展。
[摘要] 晚期肺癌患者骨转移发病率高，骨折、神经压迫、骨痛等并发症多，不仅影响患者的生活质量，而且增加了患者的经济负担及心理压力。肺癌骨转移后，癌细胞和骨组织微环境间进行复杂的相互作用，有多种相关信号通路参与其中，通过复杂的机制最终形成成骨性骨破坏、溶骨性骨破坏及混合性骨破坏。尽管目前对相关信号通路的研究取得了一定的成果，但其在调控成骨/破骨细胞分化及骨形成/骨溶解方面的确切分子机制及相互作用方式仍未阐明。随着研究的进一步深入，将会揭开肺癌骨转移后骨破坏过程的完整机制，为临床有效防治肺癌骨转移提供新的理论依据与治疗靶点。本文从溶骨性骨破坏、成骨性骨破坏和混合性骨破坏3个方面阐述近年来对肺癌骨转移后骨破坏相关信号通路的研究进展。
2018, 25(6):645-651.
DOI: 10.3872/j.issn.1007-385X.2018.06.016
Abstract:
[摘要] 持续分裂和增殖是肿瘤细胞的显著特征，为维持这一特征，肿瘤细胞的代谢发生一系列变化，包括从氧化磷酸化向有氧糖酵解转变。异柠檬酸脱氢酶（isocitrate dehydrogenase, IDH）是胞质中重要的代谢酶，除催化异柠檬酸氧化脱羧生成α-KG、产生NADPH外，还可间接调节氨基酸和脂类代谢，参与氧化应激反应等。现在越来越多的研究发现，IDH1 的表达及活性在某些肿瘤组织中发生了改变，与肿瘤的发生发展过程密切相关。本文综述了IDH1 的结构和功能，从其在肿瘤中的活性、如何参与调节氧化应激反应、突变体及与肿瘤发生相关的信号通路（HIF-1α、AKT-mTOR）等方面对IDH1 在肿瘤发生发展过程中的作用进行了阐述，并对其调控机制进行了概况总结。作为可能的肿瘤治疗新靶点，IDH1 在肿瘤发生发展中的机制研究及可能的靶向性药物的发现将是今后研究的重点。
[摘要] 持续分裂和增殖是肿瘤细胞的显著特征，为维持这一特征，肿瘤细胞的代谢发生一系列变化，包括从氧化磷酸化向有氧糖酵解转变。异柠檬酸脱氢酶（isocitrate dehydrogenase, IDH）是胞质中重要的代谢酶，除催化异柠檬酸氧化脱羧生成α-KG、产生NADPH外，还可间接调节氨基酸和脂类代谢，参与氧化应激反应等。现在越来越多的研究发现，IDH1 的表达及活性在某些肿瘤组织中发生了改变，与肿瘤的发生发展过程密切相关。本文综述了IDH1 的结构和功能，从其在肿瘤中的活性、如何参与调节氧化应激反应、突变体及与肿瘤发生相关的信号通路（HIF-1α、AKT-mTOR）等方面对IDH1 在肿瘤发生发展过程中的作用进行了阐述，并对其调控机制进行了概况总结。作为可能的肿瘤治疗新靶点，IDH1 在肿瘤发生发展中的机制研究及可能的靶向性药物的发现将是今后研究的重点。
2018, 25(6):652-655.
DOI: 10.3872/j.issn.1007-385X.2018.06.017
Abstract:
[摘要] ADP-核糖基化样因子2（ADP ribosylation factor-like protein 2，ARL2）是一种小型GTP结合蛋白，隶属于RAS超家族中的ARF家族，广泛存在于真核细胞中，在分子结构上高度保守。ARL2 参与调节微管动力学，维持细胞形态和极性；调控线粒体功能，包括线粒体形态、运动和线粒体融合等。多种肿瘤中存在ARL2 表达异常，并且改变肿瘤细胞中ARL2 表达会影响肿瘤细胞的形态、增殖和侵袭能力，影响肿瘤细胞对化疗药物的敏感性、细胞周期分布，甚至诱导细胞凋亡。本文拟对ARL2 的目前研究现状及其在肿瘤中的研究进展作一综述。
[摘要] ADP-核糖基化样因子2（ADP ribosylation factor-like protein 2，ARL2）是一种小型GTP结合蛋白，隶属于RAS超家族中的ARF家族，广泛存在于真核细胞中，在分子结构上高度保守。ARL2 参与调节微管动力学，维持细胞形态和极性；调控线粒体功能，包括线粒体形态、运动和线粒体融合等。多种肿瘤中存在ARL2 表达异常，并且改变肿瘤细胞中ARL2 表达会影响肿瘤细胞的形态、增殖和侵袭能力，影响肿瘤细胞对化疗药物的敏感性、细胞周期分布，甚至诱导细胞凋亡。本文拟对ARL2 的目前研究现状及其在肿瘤中的研究进展作一综述。
2018, 25(6):656-659.
DOI: 10.3872/j.issn.1007-385X.2018.06.018
Abstract:
[摘要] 母体胚胎亮氨酸拉链激酶（maternal embryo leucine zipper kinase ,MELK）在多数恶性肿瘤中高表达，其通过与各种类型蛋白相互作用和使其磷酸化后调节靶蛋白的生物活性，影响细胞周期调控和细胞增殖、凋亡、侵袭与转移等，促进癌细胞增殖和肿瘤形成，因此，MELK功能失调成为癌细胞逃避人体正常免疫监视的重要机制。深入了解MELK在肿瘤中的表达和作用机制，为完善肿瘤诊断分子标志物体系、肿瘤靶向治疗方案具有一定的临床意义。本文就MELK的生物学功能、对恶性肿瘤的治疗情况及其作为候选靶向分子的潜质进行综述。
[摘要] 母体胚胎亮氨酸拉链激酶（maternal embryo leucine zipper kinase ,MELK）在多数恶性肿瘤中高表达，其通过与各种类型蛋白相互作用和使其磷酸化后调节靶蛋白的生物活性，影响细胞周期调控和细胞增殖、凋亡、侵袭与转移等，促进癌细胞增殖和肿瘤形成，因此，MELK功能失调成为癌细胞逃避人体正常免疫监视的重要机制。深入了解MELK在肿瘤中的表达和作用机制，为完善肿瘤诊断分子标志物体系、肿瘤靶向治疗方案具有一定的临床意义。本文就MELK的生物学功能、对恶性肿瘤的治疗情况及其作为候选靶向分子的潜质进行综述。
联系方式
- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
- 电话：021-81871002-22
- 电子邮箱：cjcb@biother.cn
- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
- 国内定价： ￥20元/册
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.