高压氧处理胃癌AGS细胞对伊立替康耐药性的影响及其调控机制  

Effect of hyperbaric oxygen on the resistance of gastric cancer AGS cells to irinotecan and its regulatory mechanisms

作　　者：谢艳英[1] 郑紫恒 杨露露 许春进[1] Xie Yanying;Zheng Ziheng;Yang Lulu;Xu Chunjin(Department of Gastroenterology,First People’s Hospital of Shangqiu,Shangqiu 476100,China)

机构地区：[1]商丘市第一人民医院消化内科,商丘476100

出　　处：《中华航海医学与高气压医学杂志》2022年第2期225-229,共5页Chinese Journal of Nautical Medicine and Hyperbaric Medicine

摘　　要：目的探讨高压氧(HBO)处理胃癌AGS细胞对伊立替康(ITC)耐药性的影响及其调控机制。方法体外培养胃癌AGS细胞, 按照实验设计分为:对照组、HBO组、ITC组及HBO+ITC组。采用CCK-8法检测ITC联合HBO对胃癌AGS细胞增殖率的影响, 流式细胞术检测AGS细胞凋亡率的变化, Western blotting实验检测AGS细胞内凋亡及耐药相关蛋白表达量的变化。结果 HBO+ITC组AGS细胞的增殖率明显低于对照组和HBO组(P<0.01), 也低于ITC组(P<0.05)。HBO+ITC组AGS细胞凋亡率明显高于对照组和HBO组(P<0.01), 也高于ITC组(P<0.05)。ITC组和HBO+ITC组凋亡及耐药相关蛋白Bcl-2、caspase-9和P-gp在AGS细胞内的表达量明显降低, 而Bad、caspase-3和PARP表达量明显升高, 差异均有统计学意义(P<0.05或P<0.01);与对照组和HBO组比较, ITC组p-JNK表达量升高, STAT3表达量降低(P<0.01);与ITC组比较, HBO+ITC组p-JNK表达量升高, STAT3表达量降低(P<0.05或P<0.01)。结论 HBO能够协同ITC抑制胃癌AGS细胞的增殖, 通过调控JNK/STAT3信号通路影响AGS细胞凋亡, 并在一定程度上改善其耐药性。Objective To investigate the effect of hyperbaric oxygen(HBO)on the resistance of gastric cancer AGS cells to irinotecan(ITC)and its related regulatory mechanisms.Methods Gastric cancer AGS cells were cultured in vitro,and the cells were divided into four groups according to the experimental design:control group,ITC group,HBO group,and HBO+ITC group.The effect of ITC combined with HBO on the proliferation rate of gastric cancer cells was detected by Cell Counting Kit-8(CCK-8);the changes of apoptosis rate after ITC combined with HBO treatment of AGS cells were detected by flow cytometry;and the changes in the expression of apoptosis-related and drug resistance-related proteins in AGS cells were detected by Western blotting assay.Results Compared with control group and HBO group,the proliferation of AGS cells in the HBO+ITC group was further inhibited,and its proliferation rate was significantly lower than those of the control group and HBO group(P<0.01),and also lower than that of the ITC group(P<0.05).Compared with those in the control group and the HBO group,the apoptosis rate of AGS cells in the HBO+ITC group was significantly higher than those in the control group and the HBO group(P<0.01),and also higher than that in the ITC group(P<0.05).In the ITC group and HBO+ITC group,the expression of apoptosis-related and drug resistance-related proteins,including Bcl-2,caspase-9 and P-gp,were significantly decreased,while the expression of Bad,caspase-3 and PARP were significantly increased,and the differences were statistically significant(P<0.05 or P<0.01).Compared with the control group and HBO group,p-JNK expression was increased and STAT3 expression was decreased in the ITC group(P<0.01);compared with the ITC group,p-JNK expression was increased and STAT3 expression was decreased in the HBO+ITC group(P<0.05 or P<0.01).Conclusion HBO combined with ITC can effectively inhibit the proliferation of gastric cancer AGS cells,affect the apoptosis of AGS cells by regulating the JNK/STAT3 signaling pathway,and improve th

关 键 词：高压氧 伊立替康 胃癌 AGS细胞 

分 类 号：R735.2[医药卫生—肿瘤]