高压氧联合吉西他滨对人肺癌A549细胞增殖和凋亡的影响及其作用机制  

Effects of hyperbaric oxygenation combined with gemcitabine on the proliferation and apoptosis of lung cancer cells A549 and its related mechanism

作　　者：赵珂 从静 王少芳[1] 黄晓[1] 王龙[1] Zhao Ke;Cong Jing;Wang Shaofang;Huang Xiao;Wang Long(Department of Respiratory and Critical Care Medicine,Anyang People′s Hospital,Anyang 455000,China)

机构地区：[1]安阳市人民医院呼吸与危重症医学科,河南省安阳455000 [2]黄淮学院医学院

出　　处：《中华航海医学与高气压医学杂志》2019年第6期529-532,共4页Chinese Journal of Nautical Medicine and Hyperbaric Medicine

摘　　要：目的探讨高压氧(HBO)联合吉西他滨(GEM)对人肺癌A549细胞增殖和凋亡的影响及其作用机制。方法体外培养肺癌A549细胞后,实验分为4组:对照组、GEM组、HBO组和HBO+GEM组。用CCK-8检测HBO和GEM联用对肺癌A549细胞增殖的抑制作用,用流式细胞术检测A549细胞凋亡情况,Western blotting检测A549细胞凋亡相关蛋白和信号通路相关蛋白的表达水平。结果GEM组A549细胞增殖能力明显低于对照组和HBO组(P<0.05);HBO+GEM组A549细胞增殖能力明显低于GEM组(P<0.05)。GEM组A549细胞凋亡率明显高于对照组和HBO组(P<0.05);HBO+GEM组A549细胞凋亡率明显高于GEM组(P<0.05)。GEM组中Bcl-2、caspase-9表达量降低,Cyt-c、Bax、caspase-3表达量升高,Bax/Bcl-2比值升高(均P<0.01);HBO+GEM处理后,更进一步调控了凋亡相关蛋白的表达,并且降低了P-gp蛋白的表达,与GEM组比较,差异有统计学意义(P<0.05)。结论GEM组中,p-JNK表达量升高(P<0.01),而p-STAT3变化并不显著;HBO+GEM组p-STAT3的表达量降低、p-JNK表达量升高,与GEM组比较,差异有统计学意义(P<0.05)。HBO能够有效增强GEM对A549细胞的增殖抑制作用,促进GEM对A549细胞的诱导凋亡作用,还能够降低A549细胞对GEM的耐药性,其作用机制可能与调控JNK/STAT3信号通路有关。Objective To investigate the effects of hyperbaric oxygenation(HBO)combined with gemcitabine(GEM)on the proliferation and apoptosis of human lung cancer cells A549 and its related molecular mechanism.Methods Following in vitro culture of lung cancer A549 cells,the subjects were divided into the control group,the GEM group,the HBO group and the HBO+GEM group.CCK-8 was used to detect the inhibitive effects of the combined use of HBO and GEM on the proliferation of lung cancer cell A549.Flow cytometry was performed to detect apoptosis of A549,and Western blotting was used to determine the expression levels of apoptosis-related proteins and signaling pathway-associated proteins.Results The A549 proliferation capacity of the GEM group was significantly lower than that of the blank control and HBO groups(P<0.05),while that of the HBO+GEM group was significantly lower than that of the GEM group(P<0.05).The A549 apoptosis rate of the GEM group was obviously higher than that of the blank control and HBO groups(P<0.05),while that of the HBO+GEM group was significantly higher than that of the GEM group(P<0.05).The expression levels of Bcl-2 and Caspase-9 in the GEM group decreased,while the expression levels of Cyt-c,Bax and caspase-3 elevated,and Bax/Bcl-2 ratio also elevated(all P<0.01).Combined treatment with HBO and GEM further regulate the expression of apoptosis-related protein and decrease the expression of P-gp protein.As compared with the GEM group,statistical significance could be found(P<0.05).The p-JNK expression level in the GEM group was up-regulated,while the expression level of p-STAT3 was not significant(P<0.01).The p-STAT3 expression level in the HBO+GEM group was down-regulated,and the p-JNK expression level was up-regulated.Statistical significance could also be noted when compared with the GEM group(P<0.05).Conclusion HBO could effectively enhance the inhibitive effect of GEM on the proliferation of A549 cells,induce the apoptosis of A549 cells by GEM,and furthermore reduce drug resistance of A549 cells

关 键 词：高压氧 肺癌 A549细胞 吉西他滨 JNK/STAT3信号通路 

分 类 号：R734[医药卫生—肿瘤]