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Volume 27,Issue 8,2020 Table of Contents
2020, 27(8):835-842.
DOI: 10.3872/j.issn.1007-385X.2020.08.001
Abstract:
Environmental factors are important risk factor for lung cancer. Smokers are 20 times more likely to develop lung cancer than non-smokers. However, less than 20% of smokers develop lung cancer. In recent years, many studies have shown genetic polymorphism plays an important role in the development of lung cancer, mainly involving single nucleotide polymorphisms and rare highexogenous mutations. The in-depth research of the gene polymorphism will be beneficial to the screen of susceptible genes in lung cancer and genetically high-risk population, providing genetic counseling and evidence for clinically precise diagnosis and treatment. This article mainly summarizes the contents regarding genetic susceptibility of lung cancer and high-risk population screening, early diagnosis of lung cancer as well as precise medication of advanced lung cancer.
Environmental factors are important risk factor for lung cancer. Smokers are 20 times more likely to develop lung cancer than non-smokers. However, less than 20% of smokers develop lung cancer. In recent years, many studies have shown genetic polymorphism plays an important role in the development of lung cancer, mainly involving single nucleotide polymorphisms and rare highexogenous mutations. The in-depth research of the gene polymorphism will be beneficial to the screen of susceptible genes in lung cancer and genetically high-risk population, providing genetic counseling and evidence for clinically precise diagnosis and treatment. This article mainly summarizes the contents regarding genetic susceptibility of lung cancer and high-risk population screening, early diagnosis of lung cancer as well as precise medication of advanced lung cancer.
2020, 27(8):843-851.
DOI: 10.3872/j.issn.1007-385X.2020.08.002
Abstract:
With the progress of gene detection technology and the speed-up in new drug development, biological target therapy has fully covered the first-line treatment of advanced NSCLC. Immunotherapy has significantly improved the survival of advanced NSCLC patients with negative driven genes, and the median OS reaches about 2 years (15.6-30 months). EGFR is the most common driven gene. According to different EGFR mutation subtypes (L858R or 19del), different treatment mode (EGFR-TKI single drug, TKI combined with anti-vascular drugs and TKI combined with chemotherapy) is selected as the first-line treatment, which has become a consensus. Depending on the data of median PFS, the treatment efficacy against rare targets is more prominent, which has exceeded the efficacy ofstandardchemotherap:ALK(alectinib,PFS=34.8months),ROS1(ceritinib,PFS=19.3months),RET (selpercatinib, PFS=18.4 months), BRAF (dabrafenib plus trametinib, PFS=14.6 months), NTRK (larotrectinib, PFS≥12 months) and MET (savolitinib, PFS=9.7 months). In conclusion, the first-line treatment of advanced NSCLC has entered the era of“precision-targeted treatment”based on different molecular typing, and it has become a consensus that high-throughput sequencing is required for newly diagnosed patients.
With the progress of gene detection technology and the speed-up in new drug development, biological target therapy has fully covered the first-line treatment of advanced NSCLC. Immunotherapy has significantly improved the survival of advanced NSCLC patients with negative driven genes, and the median OS reaches about 2 years (15.6-30 months). EGFR is the most common driven gene. According to different EGFR mutation subtypes (L858R or 19del), different treatment mode (EGFR-TKI single drug, TKI combined with anti-vascular drugs and TKI combined with chemotherapy) is selected as the first-line treatment, which has become a consensus. Depending on the data of median PFS, the treatment efficacy against rare targets is more prominent, which has exceeded the efficacy ofstandardchemotherap:ALK(alectinib,PFS=34.8months),ROS1(ceritinib,PFS=19.3months),RET (selpercatinib, PFS=18.4 months), BRAF (dabrafenib plus trametinib, PFS=14.6 months), NTRK (larotrectinib, PFS≥12 months) and MET (savolitinib, PFS=9.7 months). In conclusion, the first-line treatment of advanced NSCLC has entered the era of“precision-targeted treatment”based on different molecular typing, and it has become a consensus that high-throughput sequencing is required for newly diagnosed patients.
FAN Shuangshuang
,
ZHANG Tingting
,
WANGTian
,
SHENG Binjie
,
YOU Fengtao
,
CHEN Dan
,
ZHAI Xiaochen
,
AN Gangli
,
MENG Huimin
,
YANG Lin
2020, 27(8):852-859.
DOI: 10.3872/j.issn.1007-385X.2020.08.003
Abstract:
Objective: To develop a new type of CD7 chimeric antigen receptor modified T cell (CD7-CAR-T) for the treatment of CD7 positive acute myeloid leukemia (AML), and to observe its killing effect on CD7 positive AML cells. Methods: The CD7-CAR lentiviral vector was constructed based on the CD7 Nanobody sequence and costimulatory domain sequence of CD28 and 4-1BB. The lentiviral particles were packaged and used to co-transfect human T cells with protein expression blocker (PEBL), so as to prepare CD7CAR-T cells. Real time cellular analysis (RTCA) was used to monitor the cytotoxicity of CD7-CAR-T cells on CD7 overexpressed 293T cells. Flow cytometry assay was used to detect the effect of CD7-CAR-T cells on proliferation and cytokine secretion of AML cells with high, medium and low CD7 expressions (KG-1, HEL and Kasumi-1 cells, respectively). Results: CD7-CAR-T cell was successfully constructed and its surface expression of CD7 was successfully blocked. Compared with T cells, CD7-CAR-T cells could significantly inhibit the proliferation of CD7-293T cells and promote the release of TNF, Granzyme B and INF-γ; in addition, CD7CAR-T cells also significantly promoted the apoptosis (t=147.1, P<0.01; t=23.57, P<0.01) and cytokine release (P<0.05 or P<0.01) in CD7 positive KG-1 and HEL cells, but had little effect on Kasumi-1 cells that only expressed minimal CD7 antigen (t=0.7058, P>0.05). Conclusion: CD7-CAR-T cells can specifically kill CD7-positiveAMLcells in vitro.
Objective: To develop a new type of CD7 chimeric antigen receptor modified T cell (CD7-CAR-T) for the treatment of CD7 positive acute myeloid leukemia (AML), and to observe its killing effect on CD7 positive AML cells. Methods: The CD7-CAR lentiviral vector was constructed based on the CD7 Nanobody sequence and costimulatory domain sequence of CD28 and 4-1BB. The lentiviral particles were packaged and used to co-transfect human T cells with protein expression blocker (PEBL), so as to prepare CD7CAR-T cells. Real time cellular analysis (RTCA) was used to monitor the cytotoxicity of CD7-CAR-T cells on CD7 overexpressed 293T cells. Flow cytometry assay was used to detect the effect of CD7-CAR-T cells on proliferation and cytokine secretion of AML cells with high, medium and low CD7 expressions (KG-1, HEL and Kasumi-1 cells, respectively). Results: CD7-CAR-T cell was successfully constructed and its surface expression of CD7 was successfully blocked. Compared with T cells, CD7-CAR-T cells could significantly inhibit the proliferation of CD7-293T cells and promote the release of TNF, Granzyme B and INF-γ; in addition, CD7CAR-T cells also significantly promoted the apoptosis (t=147.1, P<0.01; t=23.57, P<0.01) and cytokine release (P<0.05 or P<0.01) in CD7 positive KG-1 and HEL cells, but had little effect on Kasumi-1 cells that only expressed minimal CD7 antigen (t=0.7058, P>0.05). Conclusion: CD7-CAR-T cells can specifically kill CD7-positiveAMLcells in vitro.
2020, 27(8):860-866.
DOI: 10.3872/j.issn.1007-385X.2020.08.004
Abstract:
Objective: To investigate the effects of dyskerin pseudouridine synthase 1 (DKC1) on the proliferation, cell cycle and apoptosis of mucosal melanoma cells and its potential mechanisms. Methods: qPCR was used to detect the mRNAexpression of DKC1 in mucosal melanoma cell lines HMV II, GAK and normal skin cell line BJ. HMV II and GAK cells were interfered with DKC1 siRNA (si-DKC1 group) and control siRNA(si-Ctrl group) respectively; 48 h later, qPCR and Western blotting were used to verify the interference efficiency. CCK-8 assay was used to detect the effect of DKC1 knockdown on the proliferation of mucousal melanoma cells. Flow cytometry was used to detect the apoptosis and cell cycles. Western blotting and qPCR were used to detect the molecule expressions of related pathways. Results: The mRNAand protein expression levels of DKC1 in HMV II and GAK cells were significantly higher than those in BJ cells (all P<0.01). After 48 h of siRNA transfection, compared with the si-Ctrl group, the mRNA and protein levels of DKC1 in HMV II and GAK cells of the si-DKC1 group significantly reduced (all P<0.01), the cell proliferation level significantly reduced (P<0.05 or P<0.01), and the apoptosis rate of cells significantly increased (all P<0.01); in addition, the mRNAexpressions of proapoptotic molecules caspase 9, BAK and PUMA increased significantly (P<0.05 or P<0.01) and the cell cycle was blocked (P<0.05 or P<0.01); moreover, the phosphorylation levels of MEK and ERK1/2 were significantly reduced (P<0.05). Conclusion: Knockdown of DKC1 can inhibit the proliferation of mucousal melanoma cells, promote cell cycle arrest and induce apoptosis, and its mechanism may be related to MEK/ERK signal pathway.
Objective: To investigate the effects of dyskerin pseudouridine synthase 1 (DKC1) on the proliferation, cell cycle and apoptosis of mucosal melanoma cells and its potential mechanisms. Methods: qPCR was used to detect the mRNAexpression of DKC1 in mucosal melanoma cell lines HMV II, GAK and normal skin cell line BJ. HMV II and GAK cells were interfered with DKC1 siRNA (si-DKC1 group) and control siRNA(si-Ctrl group) respectively; 48 h later, qPCR and Western blotting were used to verify the interference efficiency. CCK-8 assay was used to detect the effect of DKC1 knockdown on the proliferation of mucousal melanoma cells. Flow cytometry was used to detect the apoptosis and cell cycles. Western blotting and qPCR were used to detect the molecule expressions of related pathways. Results: The mRNAand protein expression levels of DKC1 in HMV II and GAK cells were significantly higher than those in BJ cells (all P<0.01). After 48 h of siRNA transfection, compared with the si-Ctrl group, the mRNA and protein levels of DKC1 in HMV II and GAK cells of the si-DKC1 group significantly reduced (all P<0.01), the cell proliferation level significantly reduced (P<0.05 or P<0.01), and the apoptosis rate of cells significantly increased (all P<0.01); in addition, the mRNAexpressions of proapoptotic molecules caspase 9, BAK and PUMA increased significantly (P<0.05 or P<0.01) and the cell cycle was blocked (P<0.05 or P<0.01); moreover, the phosphorylation levels of MEK and ERK1/2 were significantly reduced (P<0.05). Conclusion: Knockdown of DKC1 can inhibit the proliferation of mucousal melanoma cells, promote cell cycle arrest and induce apoptosis, and its mechanism may be related to MEK/ERK signal pathway.
2020, 27(8):867-873.
DOI: 10.3872/j.issn.1007-385X.2020.08.005
Abstract:
Objective: To explore the influence of miR-339-5p on the radio-sensitivity of lung cancer A549 cells by regulating the expression of Nudix hydrolase 5 (NUDT5). Methods: X-ray-resistant lung cancer A549 cells (RA549) were induced by treatment with low concentration gradient increment combined with large dose intermittent shock in vitro. The expression level of miR-339-5p in human normal lung epithelial cells (BEAS-2B) and lung cancer cell lines (A549, L78, H1299, H460 and RA549 cells) was detected by qPCR. According to the treatment, RA549 cells were divided into NC group, 5Gy group (treatment with 5Gy X-ray), 5Gy+miR-339-5p mimic group, 5Gy+si-NUDT5 group and 5Gy+si-NUDT5+miR-339-5p inhibitor group. CCK-8 assay,Annexin V-FITC/PI double staining flow cytometry and WB were used to detect the proliferation, apoptosis and the protein expressions of NUDT5, γ-H2AX and H2AX in each group. The targeting relationship between mir-339-5p and NUDT5 was detected by Dual-luciferase reporter gene system. Results: The expression of miR-339-5p in lung cancer cell lines was significantly lower than that in BEAS-2B cells, with the lowest ex- pression level in RA549 cells (all P<0.05). NUDT5 was the target gene of miR-339-5p. Compared with the NC group, the proliferation activity and NUDT5 expression of RA549 cells in the 5 Gy group were significantly reduced (all P<0.01), and the apoptosis rate was significantly increased (P<0.01). Compared with the 5 Gy group, the proliferation activity of RA549 cells in the 5 Gy+miR-339-5p mimic group was significantly reduced (P<0.05), the apoptosis rate ([12.97±1.48]% vs [5.21±0.62]%, P<0.01) and the expression level of γ-H2AX (P<0.05) were significantly increased; the expression of NUDT5 (t=7.58, P<0.01) and cell proliferation activity (t=6.58, P< 0.01) of RA549 cells in the 5 Gy+si-NUDT5 group were significantly reduced, while the apoptosis rate ([11.21±1.06]% vs [5.54± 0.44%, P<0.01) and the expression of γ-H2AX (P<0.01) were significantly increased; and the above indicators in 5 Gy+si-NUDT5+ miR-339-5p inhibitor group showed insignificant difference from the 5 Gy group. Conclusion: Overexpression of miR-339-5p enhances the radio-sensitivity of X-ray-resistant lung cancerA549 cells by targetedly down-regulating NUDT5 expression.
Objective: To explore the influence of miR-339-5p on the radio-sensitivity of lung cancer A549 cells by regulating the expression of Nudix hydrolase 5 (NUDT5). Methods: X-ray-resistant lung cancer A549 cells (RA549) were induced by treatment with low concentration gradient increment combined with large dose intermittent shock in vitro. The expression level of miR-339-5p in human normal lung epithelial cells (BEAS-2B) and lung cancer cell lines (A549, L78, H1299, H460 and RA549 cells) was detected by qPCR. According to the treatment, RA549 cells were divided into NC group, 5Gy group (treatment with 5Gy X-ray), 5Gy+miR-339-5p mimic group, 5Gy+si-NUDT5 group and 5Gy+si-NUDT5+miR-339-5p inhibitor group. CCK-8 assay,Annexin V-FITC/PI double staining flow cytometry and WB were used to detect the proliferation, apoptosis and the protein expressions of NUDT5, γ-H2AX and H2AX in each group. The targeting relationship between mir-339-5p and NUDT5 was detected by Dual-luciferase reporter gene system. Results: The expression of miR-339-5p in lung cancer cell lines was significantly lower than that in BEAS-2B cells, with the lowest ex- pression level in RA549 cells (all P<0.05). NUDT5 was the target gene of miR-339-5p. Compared with the NC group, the proliferation activity and NUDT5 expression of RA549 cells in the 5 Gy group were significantly reduced (all P<0.01), and the apoptosis rate was significantly increased (P<0.01). Compared with the 5 Gy group, the proliferation activity of RA549 cells in the 5 Gy+miR-339-5p mimic group was significantly reduced (P<0.05), the apoptosis rate ([12.97±1.48]% vs [5.21±0.62]%, P<0.01) and the expression level of γ-H2AX (P<0.05) were significantly increased; the expression of NUDT5 (t=7.58, P<0.01) and cell proliferation activity (t=6.58, P< 0.01) of RA549 cells in the 5 Gy+si-NUDT5 group were significantly reduced, while the apoptosis rate ([11.21±1.06]% vs [5.54± 0.44%, P<0.01) and the expression of γ-H2AX (P<0.01) were significantly increased; and the above indicators in 5 Gy+si-NUDT5+ miR-339-5p inhibitor group showed insignificant difference from the 5 Gy group. Conclusion: Overexpression of miR-339-5p enhances the radio-sensitivity of X-ray-resistant lung cancerA549 cells by targetedly down-regulating NUDT5 expression.
2020, 27(8):874-878.
DOI: 10.3872/j.issn.1007-385X.2020.08.006
Abstract:
Objective: To investigate the effect of metformin on the senescence-associated secretory phenotype (SASP) of doxorubicininduced gastriccancerBGC823cells.Methods:Humangastriccancer BGC823 cells were cultured in vitro and treated with doxorubicin at gradient concentrations(50,100,150and200nmol/L).CellsenescencewasdetectedbySA-β-galstaining,and SASP factor expression was detected by ELISA. The effects of metformin on cell senescence and SASP factor secretion induced by doxorubicin (100 nmol/L) were observed by adding gradient concentrations of metformin (0, 5, 10 and 20 mmol/L). Results: With the increase of doxorubicin concentration and treatment time, the senescence rate of gastric cancer BGC823 cells increased first and then decreased. At 96 h after 100 nmol/L doxorubicin treatment, the peak aging rate reached 68.7%, accompanied with significantly increased expressions of SASP factors IL-1a, IL-6, IL-8 and CXCL1. The proportion of senescent cells was (55.2±1.9)%, (48.7±2.2)% and (40.8±2.3)% respectively under the effects of 5, 10 and 20 mmol/L metformin, which was significantly lower than that in the non-metformin treatment group (P< 0.01).At the sametime,withtheincrease of metformin concentration, the production of SASP factors IL-1α, IL-6, IL-8 and CXCL1 showed a gradient decline. Compared with the non-metformin treatment group, IL-6 and IL-8 decreased significantly under the effect of metformin above10mmol/L(P<0.05orP<0.01),whileIL-1αandCXCL1decreasedsignificantlyundertheeffectof20mmol/L metformin (all P<0.05). Conclusion: Metformin can inhibit the senescence and SASPproduction of gastric cancer cells induced by doxorubicin.
Objective: To investigate the effect of metformin on the senescence-associated secretory phenotype (SASP) of doxorubicininduced gastriccancerBGC823cells.Methods:Humangastriccancer BGC823 cells were cultured in vitro and treated with doxorubicin at gradient concentrations(50,100,150and200nmol/L).CellsenescencewasdetectedbySA-β-galstaining,and SASP factor expression was detected by ELISA. The effects of metformin on cell senescence and SASP factor secretion induced by doxorubicin (100 nmol/L) were observed by adding gradient concentrations of metformin (0, 5, 10 and 20 mmol/L). Results: With the increase of doxorubicin concentration and treatment time, the senescence rate of gastric cancer BGC823 cells increased first and then decreased. At 96 h after 100 nmol/L doxorubicin treatment, the peak aging rate reached 68.7%, accompanied with significantly increased expressions of SASP factors IL-1a, IL-6, IL-8 and CXCL1. The proportion of senescent cells was (55.2±1.9)%, (48.7±2.2)% and (40.8±2.3)% respectively under the effects of 5, 10 and 20 mmol/L metformin, which was significantly lower than that in the non-metformin treatment group (P< 0.01).At the sametime,withtheincrease of metformin concentration, the production of SASP factors IL-1α, IL-6, IL-8 and CXCL1 showed a gradient decline. Compared with the non-metformin treatment group, IL-6 and IL-8 decreased significantly under the effect of metformin above10mmol/L(P<0.05orP<0.01),whileIL-1αandCXCL1decreasedsignificantlyundertheeffectof20mmol/L metformin (all P<0.05). Conclusion: Metformin can inhibit the senescence and SASPproduction of gastric cancer cells induced by doxorubicin.
2020, 27(8):879-883.
DOI: 10.3872/j.issn.1007-385X.2020.08.007
Abstract:
Objective: To explore whether gambogic acid can enhance the sensitivity of glioma U251 cells to temozolomide and further explore its mechanism. Methods: U251 cells were cultured in vitro and divided into blank control group, gambogic acid treatment group, temozolomide alone treatment group and combined treatment group. The cells survival rates of cells in each group was detected by CCK-8 assay. Flow cytometry was used to detect cell apoptosis and changes in ROS level. Western blotting was used to detect the changes in protein expressions. Results: CCK-8 results showed that the cells survival rates of the four groups after treatment for 24 h were (98.65±3.68)%, (93.58±2.47)%, (66.81±2.39)% and (38.65±4.13)%, respectively. It can be seen that the combined treatment could significantly increase the inhibitory effect of temozolomide on U251 cells. The proportion of apoptotic U251 cells in the combined treatment group was (61.43±2.58)%, which was significantly higher than that of (26.68±1.82)% in the temozolomide-treated group. Combined treatment of gambogic acid and temozolomide could up-regulate ROS level in U251 cells, reduce the expressions of GLUT-3 and p-AKT, and inhibit the GLUT-3/AKT signaling pathway. Conclusion: Gambogic acid combined with temozolomide can enhance the sensitivity of U251 cells to temozolomide by up-regulating ROS level and inhibiting GLUT-3/AKT signaling pathway in U251 cells, and provides a theoretical basis for the application of gambogic acid in the treatment of glioma.
Objective: To explore whether gambogic acid can enhance the sensitivity of glioma U251 cells to temozolomide and further explore its mechanism. Methods: U251 cells were cultured in vitro and divided into blank control group, gambogic acid treatment group, temozolomide alone treatment group and combined treatment group. The cells survival rates of cells in each group was detected by CCK-8 assay. Flow cytometry was used to detect cell apoptosis and changes in ROS level. Western blotting was used to detect the changes in protein expressions. Results: CCK-8 results showed that the cells survival rates of the four groups after treatment for 24 h were (98.65±3.68)%, (93.58±2.47)%, (66.81±2.39)% and (38.65±4.13)%, respectively. It can be seen that the combined treatment could significantly increase the inhibitory effect of temozolomide on U251 cells. The proportion of apoptotic U251 cells in the combined treatment group was (61.43±2.58)%, which was significantly higher than that of (26.68±1.82)% in the temozolomide-treated group. Combined treatment of gambogic acid and temozolomide could up-regulate ROS level in U251 cells, reduce the expressions of GLUT-3 and p-AKT, and inhibit the GLUT-3/AKT signaling pathway. Conclusion: Gambogic acid combined with temozolomide can enhance the sensitivity of U251 cells to temozolomide by up-regulating ROS level and inhibiting GLUT-3/AKT signaling pathway in U251 cells, and provides a theoretical basis for the application of gambogic acid in the treatment of glioma.
2020, 27(8):884-888.
DOI: 10.3872/j.issn.1007-385X.2020.08.008
Abstract:
Objective: To observe the pyrolysis of colorectal cancer Lovo cells overexpressing Gasdermin E (GSDME) after the treatment with oxaliplatin. Methods: The expression level of GSDME gene in colorectal cancer Lovo cells and normal colorectal epithelial HCOEPIC cells was detected by qPCR. The GSDME-WT (wild-type GSDME) and GSDME-D270A (mutant GSDME) recombinant plasmids were constructed. The plasmids were packaged as lentivirus and then transfected into Lovo cells to construct Lovo cell line with stable and high expression of GSDME. Western blotting was used to detect the expression level of GSDME in cells of WT, D270A and empty vector groups. Different concentrations of oxaliplatin (0, 4, 8, 16, 32, 64 μg/ml) were applied to treat Lovo cells and HCOEPIC cells in WT and D270Agroups, and the morphological changes of the cells were observed under a microscope. Results: The expression of GSDME in HCOEPIC cells was significantly higher than that in Lovo cells (P<0.01). GSDME-WT and GSDME-D270A plasmids with high GSDME expression and the corresponding Lovo cell lines were successfully constructed. Compared with the empty vector group, the expression level of GSDME in Lovo cells of WT and D270A groups were significantly increased (all P<0.05). Observation under the microscope showed that after being treated with 64 μg/ml oxaliplatin for 9 and 12 hours, the volume of Lovo cells and HCOEPIC cells in WT group gradually increased and“blistered”to one side and showed obvious pyrolysis phenomenon. The pyrolysis rate of cells in WT group was significantly higher than that of the control group without oxaliplatin treatment (Lovo cells: [7.405± 1.010]% vs [3.441±0.401]%, P<0.05; HCOEPIC cells: [7.203±1.020]% vs [4.201±0.302]%, P<0.05). Conclusion: Oxaliplatin pro-motes the pyrolysis of colorectal cancer Lovo cells overexpressing GSDME gene.
Objective: To observe the pyrolysis of colorectal cancer Lovo cells overexpressing Gasdermin E (GSDME) after the treatment with oxaliplatin. Methods: The expression level of GSDME gene in colorectal cancer Lovo cells and normal colorectal epithelial HCOEPIC cells was detected by qPCR. The GSDME-WT (wild-type GSDME) and GSDME-D270A (mutant GSDME) recombinant plasmids were constructed. The plasmids were packaged as lentivirus and then transfected into Lovo cells to construct Lovo cell line with stable and high expression of GSDME. Western blotting was used to detect the expression level of GSDME in cells of WT, D270A and empty vector groups. Different concentrations of oxaliplatin (0, 4, 8, 16, 32, 64 μg/ml) were applied to treat Lovo cells and HCOEPIC cells in WT and D270Agroups, and the morphological changes of the cells were observed under a microscope. Results: The expression of GSDME in HCOEPIC cells was significantly higher than that in Lovo cells (P<0.01). GSDME-WT and GSDME-D270A plasmids with high GSDME expression and the corresponding Lovo cell lines were successfully constructed. Compared with the empty vector group, the expression level of GSDME in Lovo cells of WT and D270A groups were significantly increased (all P<0.05). Observation under the microscope showed that after being treated with 64 μg/ml oxaliplatin for 9 and 12 hours, the volume of Lovo cells and HCOEPIC cells in WT group gradually increased and“blistered”to one side and showed obvious pyrolysis phenomenon. The pyrolysis rate of cells in WT group was significantly higher than that of the control group without oxaliplatin treatment (Lovo cells: [7.405± 1.010]% vs [3.441±0.401]%, P<0.05; HCOEPIC cells: [7.203±1.020]% vs [4.201±0.302]%, P<0.05). Conclusion: Oxaliplatin pro-motes the pyrolysis of colorectal cancer Lovo cells overexpressing GSDME gene.
2020, 27(8):889-894.
DOI: 10.3872/j.issn.1007-385X.2020.08.009
Abstract:
Objective: To observe the effects of shikonin on the proliferation, apoptosis and cell cycle of human esophageal carcinoma TE-1 cells, and to explore its mechanism. Methods: TE-1 cells were treated with different concentrations of shikonin (0, 1, 5, 10 μmol/L). MTT assay was used to detect cell proliferation at different time points (24, 48 and 72 h). After treatment with shikonin for 48 h, cell apoptosis in TE-1 cells of each group was observed with Hoechst 33258 fluorescence staining. Flow cytometry was used to detect apoptosis and cell cycle. The changes in expression of TRAP1/Akt/mTOR signaling pathway related proteins were detected by Western blotting. Results: Shikonin inhibited the proliferation of TE-1 cells in a time-dose-dependent manner (P<0.05 or P<0.01). Compared with the control group, shikonin significantly promoted the apoptosis of TE-1 cells (P<0.01), induced the G0/G1 phase block of TE-1 cells (P<0.05 or P<0.01), and reduced the expression levels of TRAP1, p-Akt and p-MTOR (P<0.05 or P<0.01). The above effects were all dose-dependent. Conclusion: Shikonin can significantly inhibit the proliferation of TE-1 cells in vitro, induce G0/G1 phase arrest and promote apoptosis, which may be closely related to the inhibition of TRAP1/Akt/mTOR signaling pathway.
Objective: To observe the effects of shikonin on the proliferation, apoptosis and cell cycle of human esophageal carcinoma TE-1 cells, and to explore its mechanism. Methods: TE-1 cells were treated with different concentrations of shikonin (0, 1, 5, 10 μmol/L). MTT assay was used to detect cell proliferation at different time points (24, 48 and 72 h). After treatment with shikonin for 48 h, cell apoptosis in TE-1 cells of each group was observed with Hoechst 33258 fluorescence staining. Flow cytometry was used to detect apoptosis and cell cycle. The changes in expression of TRAP1/Akt/mTOR signaling pathway related proteins were detected by Western blotting. Results: Shikonin inhibited the proliferation of TE-1 cells in a time-dose-dependent manner (P<0.05 or P<0.01). Compared with the control group, shikonin significantly promoted the apoptosis of TE-1 cells (P<0.01), induced the G0/G1 phase block of TE-1 cells (P<0.05 or P<0.01), and reduced the expression levels of TRAP1, p-Akt and p-MTOR (P<0.05 or P<0.01). The above effects were all dose-dependent. Conclusion: Shikonin can significantly inhibit the proliferation of TE-1 cells in vitro, induce G0/G1 phase arrest and promote apoptosis, which may be closely related to the inhibition of TRAP1/Akt/mTOR signaling pathway.
2020, 27(8):895-902.
DOI: 10.3872/j.issn.1007-385X.2020.08.010
Abstract:
Objective:To detect the expression of transcription factor FOXP4 (Forkhead box P4) in laryngeal squamous cell carcinoma (LSCC) tissues and cell lines, and to investigate its effects on the proliferation, migration, invasion, cell cycle, and apoptosis of LSCC TU177 cells in vitro as well as to explore its relationship with epithelial-mesenchymal transition (EMT) process. Methods: A total of 40 pairs of tumor tissues and adjacent tissues that resected from LSCC patients were collected from the biological specimen bank of the Forth Hospital of Hebei Medical University between 2013 and 2015. The expression of FOXP4 in LSCC tissues and corresponding adjacent tissues was detected by qPCR. qPCR and Western blotting were used to detect the FOXP4 expression level in human LSCC cell lines (AMC-HN-8, TU177, TU686, and TU212). Small interfering RNA (si-RNA) was used to knock down FOXP4 expression in TU177 cells. The effects of FOXP4 knockdown on the proliferation, migration, invasion, cell cycle and apoptosis of TU177 cells were measured by MTS assay, clone formation assay, Transwell chamber migration and invasion assay, and flow cytometry, respectively. The mRNA levels of EMT markers N-cadherin, β-catenin, Vimentin, Twist, Snail and zine finger E box binding homeobox 1 (ZEB1) after transfection of si-FOXP4 in TU177 cells were detected by qPCR. The changes of protein levels of N-cadherin, β-catenin, Vimentin and Twist afterFOXP4knockdownweremeasuredbyWesternblotting.Results:TheexpressionofFOXP4in LSCC tissues was significantly higher than that in adjacent tissues (P<0.05), and it was related to the TNM stage of tumors and lymph node metastasis (all P<0.05). The expression of FOXP4 in LSCC cells was higher than that in the adjacent tissues (P<0.05 or P<0.01). The expression of FOXP4 in TU177 cells transfected with si-FOXP4 was significantly lower than that in the control group (P<0.01). Compared with the control group, knocking down FOXP4 could inhibit the proliferation, migration and invasion but promote the apoptosis of TU177 cells in vitro (all P<0.01), block the cell cycle at G0/G1 phase (P<0.01), and reduce cell replication in S phase (P<0.01); in addition, knocking down FOXP4 could reduce the mRNA levels of N-cadherin, β-catenin, Vimentin, Twist, Snail, ZEB1 (P<0.05 or P<0.01) and the protein levels of N-cadherin, β-catenin, Vimentin, Twist in TU177 cells. Conclusion: The high expression of FOXP4 may be related to the occurrence and development of LSCC. FOXP4 knockdown can inhibit the proliferation, migration and invasion of laryngeal cancer cells in vitro, block cell cycle at G0/G1 phase, promote apoptosis, and may participate in the EMT process.
Objective:To detect the expression of transcription factor FOXP4 (Forkhead box P4) in laryngeal squamous cell carcinoma (LSCC) tissues and cell lines, and to investigate its effects on the proliferation, migration, invasion, cell cycle, and apoptosis of LSCC TU177 cells in vitro as well as to explore its relationship with epithelial-mesenchymal transition (EMT) process. Methods: A total of 40 pairs of tumor tissues and adjacent tissues that resected from LSCC patients were collected from the biological specimen bank of the Forth Hospital of Hebei Medical University between 2013 and 2015. The expression of FOXP4 in LSCC tissues and corresponding adjacent tissues was detected by qPCR. qPCR and Western blotting were used to detect the FOXP4 expression level in human LSCC cell lines (AMC-HN-8, TU177, TU686, and TU212). Small interfering RNA (si-RNA) was used to knock down FOXP4 expression in TU177 cells. The effects of FOXP4 knockdown on the proliferation, migration, invasion, cell cycle and apoptosis of TU177 cells were measured by MTS assay, clone formation assay, Transwell chamber migration and invasion assay, and flow cytometry, respectively. The mRNA levels of EMT markers N-cadherin, β-catenin, Vimentin, Twist, Snail and zine finger E box binding homeobox 1 (ZEB1) after transfection of si-FOXP4 in TU177 cells were detected by qPCR. The changes of protein levels of N-cadherin, β-catenin, Vimentin and Twist afterFOXP4knockdownweremeasuredbyWesternblotting.Results:TheexpressionofFOXP4in LSCC tissues was significantly higher than that in adjacent tissues (P<0.05), and it was related to the TNM stage of tumors and lymph node metastasis (all P<0.05). The expression of FOXP4 in LSCC cells was higher than that in the adjacent tissues (P<0.05 or P<0.01). The expression of FOXP4 in TU177 cells transfected with si-FOXP4 was significantly lower than that in the control group (P<0.01). Compared with the control group, knocking down FOXP4 could inhibit the proliferation, migration and invasion but promote the apoptosis of TU177 cells in vitro (all P<0.01), block the cell cycle at G0/G1 phase (P<0.01), and reduce cell replication in S phase (P<0.01); in addition, knocking down FOXP4 could reduce the mRNA levels of N-cadherin, β-catenin, Vimentin, Twist, Snail, ZEB1 (P<0.05 or P<0.01) and the protein levels of N-cadherin, β-catenin, Vimentin, Twist in TU177 cells. Conclusion: The high expression of FOXP4 may be related to the occurrence and development of LSCC. FOXP4 knockdown can inhibit the proliferation, migration and invasion of laryngeal cancer cells in vitro, block cell cycle at G0/G1 phase, promote apoptosis, and may participate in the EMT process.
2020, 27(8):903-910.
DOI: 10.3872/j.issn.1007-385X.2020.08.011
Abstract:
Objective: Bioinformatics combined with Gene Expression Omnibus (GEO) was used to screen key genes involved in the development of gastric cancer in order to obtain molecular markers for diagnosis, target selection and prognosis prediction of gastric cancer. Methods:Thechipdatasetsrelatedtogastriccancer(GC)fromtheGEOdatabase were downloaded, and differentially expressed genes (DEG) were screened. Functional enrichment analysis on DEG was performed, and protein-protein interaction network (PPI) was constructed to screenkeygenes.Then,co-expressionnetworkswerefurtherconstructed,andsurvival curves were drawn and hierarchical clustering analysis was performed. Results: A total of 261 GC-related DEGs were selected, and 14 key genes were obtained through analysis, which were PLOD1, PLOD3, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL8A1, COL12A1, COL15A1, ITGA2, LUM and SERPINH1. Key genes are mainly involved in biological processes such as generation of collagen fiber tissues, extracellular matrix tissues, extracellular structure tissues, skin morphogenesis, collagen biosynthesis and vascular development. Survival curve analysis showed that the change in the expression of COL3A1 (P=0.0241) significantly reduced the overall survival rate of patients with gastric cancer; the change in the expression of ITGA2 (P=0.0679) also showed a correlation with the reduction of diseasefree survival in gastric cancer patients. Compared with normal gastric tissues, hierarchical cluster analysis showed that the expressions of genes PLOD1, PLOD3, COL3A1, ITGA2, COL1A2, COL1A1, COL4A1, LUM, COL12A1, SERPINH1 and COL8A1 in GC tissues were up-regulated. Conclusion: The key genes obtained after screening can be used as potential molecular markers for early diagnosis, treatment target selection and prognosis judgment of gastric cancer, which provide reference for subsequent research.
Objective: Bioinformatics combined with Gene Expression Omnibus (GEO) was used to screen key genes involved in the development of gastric cancer in order to obtain molecular markers for diagnosis, target selection and prognosis prediction of gastric cancer. Methods:Thechipdatasetsrelatedtogastriccancer(GC)fromtheGEOdatabase were downloaded, and differentially expressed genes (DEG) were screened. Functional enrichment analysis on DEG was performed, and protein-protein interaction network (PPI) was constructed to screenkeygenes.Then,co-expressionnetworkswerefurtherconstructed,andsurvival curves were drawn and hierarchical clustering analysis was performed. Results: A total of 261 GC-related DEGs were selected, and 14 key genes were obtained through analysis, which were PLOD1, PLOD3, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL8A1, COL12A1, COL15A1, ITGA2, LUM and SERPINH1. Key genes are mainly involved in biological processes such as generation of collagen fiber tissues, extracellular matrix tissues, extracellular structure tissues, skin morphogenesis, collagen biosynthesis and vascular development. Survival curve analysis showed that the change in the expression of COL3A1 (P=0.0241) significantly reduced the overall survival rate of patients with gastric cancer; the change in the expression of ITGA2 (P=0.0679) also showed a correlation with the reduction of diseasefree survival in gastric cancer patients. Compared with normal gastric tissues, hierarchical cluster analysis showed that the expressions of genes PLOD1, PLOD3, COL3A1, ITGA2, COL1A2, COL1A1, COL4A1, LUM, COL12A1, SERPINH1 and COL8A1 in GC tissues were up-regulated. Conclusion: The key genes obtained after screening can be used as potential molecular markers for early diagnosis, treatment target selection and prognosis judgment of gastric cancer, which provide reference for subsequent research.
2020, 27(8):911-919.
DOI: 10.3872/j.issn.1007-385X.2020.08.012
Abstract:
Objective: To investigate the effect of exosomes derived from osteosarcoma on the differentiation of tumor-related macrophagesanditsmechanism.Methods:FromMarch2018toOctober2019,tumortissuesandcorrespondingnormaltissuesfrom18patients with primary osteosarcoma who underwent osteosarcoma resection and pathological diagnosis in the Departments of Orthopedics and Pediatric Surgery of theAffiliated HospitalofNorthSichuanMedicalCollegewerecollected. The expression level of Tim-3 was detected by Western blotting; Exosomes of osteosarcoma MG63 cells (MG63-Exo) were isolated and identified by transmission electron microscopy and nanoparticle size analysis, and its phagocytosis by macrophages was verified by Dual fluorescent staining; The effects of MG63-Exo on macrophage differentiation and the expression levels of IL-10, TGF-β and VEGF were detected by qPCR; The effects of MG63-Exo induced macrophages on the migration and invasion of MG63 cells and the expression of EMT related proteins were detected by Transwell invasion and migration assay and Western blotting; CRISPR/cas9 was used to knock out Tim-3 in MG63 cells, and its knockout efficiency was verified by Western blotting, and then qPCR, transwell assay and Western blotting were used to detect the effect of MG63-Exo with Tim-3 knock-out on macrophage differentiation, as well as migration, invasion and expression of EMT related proteins in MG63 cells; Finally, the mouse model of osteosarcoma lung metastasis was used to verify the effect of exosomes from different sources on the lung metastasis of osteosarcoma. Results: Transmission electron microscopy and nanoparticle size assay confirmed that MG63-Exo were successfully isolated, and Confocal fluorescence results confirmed that it could be phagocytized by macrophages; qPCR results showed that MG63-Exo significantly promoted M2 differentiation of macrophages compared with PBS (P<0.05); Compared with PBS control group, M2 macrophages induced by MG63-Exo significantly promoted the migration, invasion and EMT of osteosarcoma cells (all P<0.05); The mRNA and protein expressions of Tim-3 in the MG63 cells knocked out by CRISPR/ cas9 (Tim-3-KO) were significantly reduced (all P<0.05), and Tim-3 could be transferred into macrophages in the form of exosomes; Compared with MG63-Exo co-cultured macrophages, the M2 type differentiation of macrophages treated with Tim-3-KO-exo was significantly decreased (P<0.05); Compared with the MG63 cells co-cultured with macrophages induced by MG63-Exo, the migration, invasion and EMT were significantly reduced while the lung metastasis was significantly promoted in MG63 cells co-cultured with macrophages induced by Tim-3-KO-Exo (all P<0.05). Conclusion: Exosomes derived from osteosarcoma can induce M2 polarization of macrophages through Tim-3 and promote the invasion and metastasis of tumor.
Objective: To investigate the effect of exosomes derived from osteosarcoma on the differentiation of tumor-related macrophagesanditsmechanism.Methods:FromMarch2018toOctober2019,tumortissuesandcorrespondingnormaltissuesfrom18patients with primary osteosarcoma who underwent osteosarcoma resection and pathological diagnosis in the Departments of Orthopedics and Pediatric Surgery of theAffiliated HospitalofNorthSichuanMedicalCollegewerecollected. The expression level of Tim-3 was detected by Western blotting; Exosomes of osteosarcoma MG63 cells (MG63-Exo) were isolated and identified by transmission electron microscopy and nanoparticle size analysis, and its phagocytosis by macrophages was verified by Dual fluorescent staining; The effects of MG63-Exo on macrophage differentiation and the expression levels of IL-10, TGF-β and VEGF were detected by qPCR; The effects of MG63-Exo induced macrophages on the migration and invasion of MG63 cells and the expression of EMT related proteins were detected by Transwell invasion and migration assay and Western blotting; CRISPR/cas9 was used to knock out Tim-3 in MG63 cells, and its knockout efficiency was verified by Western blotting, and then qPCR, transwell assay and Western blotting were used to detect the effect of MG63-Exo with Tim-3 knock-out on macrophage differentiation, as well as migration, invasion and expression of EMT related proteins in MG63 cells; Finally, the mouse model of osteosarcoma lung metastasis was used to verify the effect of exosomes from different sources on the lung metastasis of osteosarcoma. Results: Transmission electron microscopy and nanoparticle size assay confirmed that MG63-Exo were successfully isolated, and Confocal fluorescence results confirmed that it could be phagocytized by macrophages; qPCR results showed that MG63-Exo significantly promoted M2 differentiation of macrophages compared with PBS (P<0.05); Compared with PBS control group, M2 macrophages induced by MG63-Exo significantly promoted the migration, invasion and EMT of osteosarcoma cells (all P<0.05); The mRNA and protein expressions of Tim-3 in the MG63 cells knocked out by CRISPR/ cas9 (Tim-3-KO) were significantly reduced (all P<0.05), and Tim-3 could be transferred into macrophages in the form of exosomes; Compared with MG63-Exo co-cultured macrophages, the M2 type differentiation of macrophages treated with Tim-3-KO-exo was significantly decreased (P<0.05); Compared with the MG63 cells co-cultured with macrophages induced by MG63-Exo, the migration, invasion and EMT were significantly reduced while the lung metastasis was significantly promoted in MG63 cells co-cultured with macrophages induced by Tim-3-KO-Exo (all P<0.05). Conclusion: Exosomes derived from osteosarcoma can induce M2 polarization of macrophages through Tim-3 and promote the invasion and metastasis of tumor.
2020, 27(8):920-926.
DOI: 10.3872/j.issn.1007-385X.2020.08.013
Abstract:
Objective: To study the expression of miRNA-95 in osteosarcoma tissues and cell lines, as well as to reveal its effect on proliferation, apoptosis, cell cycle and invasion ability of osteosarcoma cells. Methods: Real-time fluorescent quantitative PCR was used to detect the expression of miRNA-95 in 15 pairs of osteosarcoma tissues and their adjacent normal tissues (specimens were collected from patients underwent surgery in Qingdao Haici Medical Group from January 2015 to January 2018), osteosarcoma cell lines (MG-63, U2OS, 143B and HOS) and normal human osteoblast hFOB1.19 cell line. miRNA-95 mimics and miRNA-95 inhibitors were respectively transfected into MG-63 cells by Lipofectamine 2000, and miRNA-NC group was set up as control group. CCK-8 method was used to detect the changes in cell proliferation, Flow cytometry was used to detect the changes in cell cycle and apoptosis, Transwell method was used to detect the changes in cell invasion ability, and Dual luciferase enzyme activity assay was used to detect and validate the target gene of miRNA-95 in osteosarcoma cells. Results: The expression level of miRNA-95 in human osteosarcoma tissues and cell lines (MG-63, U2OS, 143B and HOS) was significantly higher than that in adjacent tissues and normal human osteoblast hFOB1.19 cell line (all P<0.01), with the highest expression in MG-63 cells (P<0.01). Compared with the miRNA-NC group, the proliferation and invasion abilities of MG-63 cells in miRNA-95 mimics group increased significantly, while the apoptosis rate decreased significantly (all P<0.01). However, the proliferation and invasion activities of MG-63 cells in miRNA-95 inhibitor group decreased significantly, while the apoptosis rate increased significantly, and the cell cycle was obviously blocked (all P<0.01). miRNA-95 played a role in targeting the gene of epithelialmembraneprotein1 (EMP-1) in human osteosarcoma MG-63 cells. Conclusion: miRNA-95 is highly expressed in human osteosarcoma tissues and cells; inhibitor of miRNA-95 expression can promote apoptosis and inhibit proliferation, cell cycle and invasion of osteosarcoma cells, which may be related with targeting EMP-1 gene.
Objective: To study the expression of miRNA-95 in osteosarcoma tissues and cell lines, as well as to reveal its effect on proliferation, apoptosis, cell cycle and invasion ability of osteosarcoma cells. Methods: Real-time fluorescent quantitative PCR was used to detect the expression of miRNA-95 in 15 pairs of osteosarcoma tissues and their adjacent normal tissues (specimens were collected from patients underwent surgery in Qingdao Haici Medical Group from January 2015 to January 2018), osteosarcoma cell lines (MG-63, U2OS, 143B and HOS) and normal human osteoblast hFOB1.19 cell line. miRNA-95 mimics and miRNA-95 inhibitors were respectively transfected into MG-63 cells by Lipofectamine 2000, and miRNA-NC group was set up as control group. CCK-8 method was used to detect the changes in cell proliferation, Flow cytometry was used to detect the changes in cell cycle and apoptosis, Transwell method was used to detect the changes in cell invasion ability, and Dual luciferase enzyme activity assay was used to detect and validate the target gene of miRNA-95 in osteosarcoma cells. Results: The expression level of miRNA-95 in human osteosarcoma tissues and cell lines (MG-63, U2OS, 143B and HOS) was significantly higher than that in adjacent tissues and normal human osteoblast hFOB1.19 cell line (all P<0.01), with the highest expression in MG-63 cells (P<0.01). Compared with the miRNA-NC group, the proliferation and invasion abilities of MG-63 cells in miRNA-95 mimics group increased significantly, while the apoptosis rate decreased significantly (all P<0.01). However, the proliferation and invasion activities of MG-63 cells in miRNA-95 inhibitor group decreased significantly, while the apoptosis rate increased significantly, and the cell cycle was obviously blocked (all P<0.01). miRNA-95 played a role in targeting the gene of epithelialmembraneprotein1 (EMP-1) in human osteosarcoma MG-63 cells. Conclusion: miRNA-95 is highly expressed in human osteosarcoma tissues and cells; inhibitor of miRNA-95 expression can promote apoptosis and inhibit proliferation, cell cycle and invasion of osteosarcoma cells, which may be related with targeting EMP-1 gene.
2020, 27(8):927-937.
DOI: 10.3872/j.issn.1007-385X.2020.08.014
Abstract:
环状RNA是一类通过特殊成环机制形成的具有相对稳定结构的RNA，广泛存在于真核细胞中。环状RNA在众多病 理生理过程中发挥重要作用，包括肿瘤的发生发展。原发性肝癌的发病率和病死率在全球肿瘤发生和死亡中均居前列，探索环 状RNA在原发性肝癌中的作用将丰富对原发性肝癌的发生发展及防治的了解。有不少研究表明环状RNA参与原发性肝癌的发 生发展及预后，本文就环状RNA的产生及功能，及其在原发性肝癌中的作用进行综述，为原发性肝癌的早期诊断、预后预测及治 疗靶点选择提供依据。
环状RNA是一类通过特殊成环机制形成的具有相对稳定结构的RNA，广泛存在于真核细胞中。环状RNA在众多病 理生理过程中发挥重要作用，包括肿瘤的发生发展。原发性肝癌的发病率和病死率在全球肿瘤发生和死亡中均居前列，探索环 状RNA在原发性肝癌中的作用将丰富对原发性肝癌的发生发展及防治的了解。有不少研究表明环状RNA参与原发性肝癌的发 生发展及预后，本文就环状RNA的产生及功能，及其在原发性肝癌中的作用进行综述，为原发性肝癌的早期诊断、预后预测及治 疗靶点选择提供依据。
2020, 27(8):938-945.
DOI: 10.3872/j.issn.1007-385X.2020.08.015
Abstract:
Wnt/β-catenin信号通路在胚胎发育、细胞周期、炎症反应和肿瘤形成等过程中具有不可或缺的作用。在消化道肿瘤 中，存在Wnt/β-catenin信号通路的显著异常激活。随着对Wnt/β-catenin信号通路的深入了解，Wnt/β-catenin信号通路抑制剂的 研发也取得了显著的成效，已有部分Wnt/β-catenin信号通路抑制剂在临床试验中显示出良好的抗肿瘤效果。并且，一些最初用 于治疗其他疾病的药物最近被发现可阻断Wnt/β-catenin信号通路，提示它们在治疗Wnt/β-catenin依赖性癌症中的潜力。本文对 Wnt/β-catenin信号通路抑制剂在消化道肿瘤中作用的研究现状进行简要概述。
Wnt/β-catenin信号通路在胚胎发育、细胞周期、炎症反应和肿瘤形成等过程中具有不可或缺的作用。在消化道肿瘤 中，存在Wnt/β-catenin信号通路的显著异常激活。随着对Wnt/β-catenin信号通路的深入了解，Wnt/β-catenin信号通路抑制剂的 研发也取得了显著的成效，已有部分Wnt/β-catenin信号通路抑制剂在临床试验中显示出良好的抗肿瘤效果。并且，一些最初用 于治疗其他疾病的药物最近被发现可阻断Wnt/β-catenin信号通路，提示它们在治疗Wnt/β-catenin依赖性癌症中的潜力。本文对 Wnt/β-catenin信号通路抑制剂在消化道肿瘤中作用的研究现状进行简要概述。
2020, 27(8):946-950.
DOI: 10.3872/j.issn.1007-385X.2020.08.016
Abstract:
近年来，免疫治疗在全球恶性肿瘤治疗中取得了备受瞩目的成绩，新型免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）不断被研发并拓展于临床实践中。中国自主研发的多款程序性死亡分子1（programmed death 1，PD-1）抑制剂也 相继在临床应用中取得了令人振奋的疗效。特瑞普利单抗（toripalimab，JS001，商品名为拓益）是我国自主研发的首个获批上 市的国产PD-1抑制剂，基于其良好的疗效及安全性，该药于2018年12月17日获得国家药品监督管理局（National Medical ProductsAdministration，NMPA）批准上市，用于既往接受标准治疗失败的局部进展或转移性黑色素瘤的治疗。此外，特瑞普利单抗在 鼻咽癌（nasopharyngeal carcinoma，NPC）、尿路上皮癌（urothelial carcinoma，UC）和非小细胞肺癌（non-small cell lung cancer， NSCLC）等多种实体瘤中的临床试验也相继被开展并取得喜人的疗效。本文就特瑞普利单抗的作用机制、药效学、药代动力学、 临床研究、不良反应及疗效预测标志物等方面的最新进展进行梳理，以期为临床应用提供参考依据。
近年来，免疫治疗在全球恶性肿瘤治疗中取得了备受瞩目的成绩，新型免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）不断被研发并拓展于临床实践中。中国自主研发的多款程序性死亡分子1（programmed death 1，PD-1）抑制剂也 相继在临床应用中取得了令人振奋的疗效。特瑞普利单抗（toripalimab，JS001，商品名为拓益）是我国自主研发的首个获批上 市的国产PD-1抑制剂，基于其良好的疗效及安全性，该药于2018年12月17日获得国家药品监督管理局（National Medical ProductsAdministration，NMPA）批准上市，用于既往接受标准治疗失败的局部进展或转移性黑色素瘤的治疗。此外，特瑞普利单抗在 鼻咽癌（nasopharyngeal carcinoma，NPC）、尿路上皮癌（urothelial carcinoma，UC）和非小细胞肺癌（non-small cell lung cancer， NSCLC）等多种实体瘤中的临床试验也相继被开展并取得喜人的疗效。本文就特瑞普利单抗的作用机制、药效学、药代动力学、 临床研究、不良反应及疗效预测标志物等方面的最新进展进行梳理，以期为临床应用提供参考依据。
2020, 27(8):951-953.
DOI: 10.3872/j.issn.1007-385X.2020.08.017
Abstract:
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- 《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
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- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.