右美托咪定对顺铂诱导的非小细胞肺癌细胞凋亡及氧化应激的影响

Effects of Dexmedetomidine on Cisplatin-induced Apoptosis and Oxidative Stress inNon-small Cell Lung Cancer Cells

目的探讨右美托咪定(Dex)对顺铂诱导的人非小细胞肺癌(NSCLC)细胞凋亡的影响及其潜在机制。方法将人非小细胞肺癌细胞系分为3组:对照组、顺铂组和Dex组。采用Western Blot法检测各组细胞中凋亡相关蛋白、细胞色素C、mTOR/ERK1/2信号分子及E-钙粘蛋白的表达,采用试剂盒法检测活性氧(ROS)的含量。结果与对照组相比,顺铂组和Dex组Caspase 3、Caspase 9和Bax的表达显著增加(P<0.05),Dex组高于顺铂组(P<0.05)。与对照组相比,顺铂组和Dex组Bcl-2表达显著降低(P<0.05),顺铂组和Dex组间比较无显著差异。与对照组相比,顺铂组和Dex组ROS的含量及细胞色素C的释放显著增加(P<0.05),Dex组高于顺铂组(P<0.05)。Dex组p-mTOR和E-钙粘蛋白的表达显著低于对照组和顺铂组(P<0.05),对照组和顺铂组间比较无显著差异。与对照组相比,顺铂组和Dex组p-ERK1/2的表达显著降低(P<0.05),Dex组低于顺铂组(P<0.05)。各组间mTOR和ERK1/2的表达无显著差异。结论Dex可进一步促进顺铂诱导的肺癌细胞凋亡,机制可能与其抑制mTOR和ERK1/2增殖信号通路的活性及抑制E-钙粘蛋白的表达有关。

Objective To investigate the effect of dexmedetomidine(Dex)on cisplatin-induced apoptosis in human non-small cell lung cancer(NSCLC)cells and its underlying mechanism.Methods Human NSCLC cells were divided into 3 groups:the control group,cisplatin group and Dex group.Western blot was used to detect the expression of apoptosis-related protein,cytochrome C,mTOR/ERK1/2 signaling molecule and E-cadherin in each group.The content of reactive oxygen species(ROS)was detected by kit method.Results Compared with the control group,the expression of Caspase 3,Caspase 9 and Bax in the cisplatin group and the Dex group was significantly increased(P<0.05),and the Dex group was higher than the cisplatin group(P<0.05).Compared with the control group,the expression of Bcl-2 was significantly lower in the cisplatin group and the Dex group(P<0.05),and there was no significant difference between the cisplatin group and the Dex group.Compared with the control group,ROS content and cytochrome C release were significantly increased in the cisplatin group and the Dex group(P<0.05),and the Dex group was higher than the cisplatin group(P<0.05).The expression of p-mTOR and E-cadherin in the Dex group was significantly lower than that in the control group and the cisplatin group(P<0.05).There was no significant difference between the control group and the cisplatin group.Compared with the control group,the expression of p-ERK1/2 was significantly lower in the cisplatin group and the Dex group(P<0.05),and the Dex group was lower than the cisplatin group(P<0.05).There was no significant difference in the expression of mTOR and ERK1/2 between the groups.Conclusion Dex can further promote the apoptosis of lung cancer cells induced by cisplatin,which may be related to the inhibition of mTOR and ERK1/2 proliferation signaling pathway and the inhibition of E-cadherin expression.