Smac多肽对肺腺癌耐药性的作用机制研究

Studies on the Regulation Mechanism of Smac Polypeptide on Drug Resistance in Lung Adenocarcinoma

目的探讨Smac多肽对肺腺癌细胞耐药性的影响及作用机制。方法培养肺腺癌细胞株A549并诱导产生耐紫杉醇耐药A549/Taxol细胞,分为用Smac多肽处理的观察组及用Smac反向多肽处理的对照组。记录两组细胞增殖活力、细胞内凋亡基因表达量及细胞内耐药基因表达量。结果两组培养12 h、18 h、24 h的细胞增殖活力比较差异均有统计学意义(P<0.05)。与对照组比较,细胞培养24 h后,观察组细胞内Livin、X连锁凋亡抑制蛋白、多耐药基因、肺耐药相关蛋白、拓扑异构酶Ⅱ、谷胱甘肽-s-转移酶-π的mRNA表达量均显著降低,含半胱氨酸的天冬氨酸蛋白水解酶(Caspase)-3、Caspase-7、Caspase-9的mRNA表达量均显著升高,比较差异有统计学意义(P<0.05)。结论 Smac多肽通过下调凋亡抑制蛋白及耐药基因的表达来改善肺腺癌细胞的紫杉醇耐药性。

Objective To study the effect and mechanism of Smac polypeptide on drug resistance of lung adenocarcinoma cells. Methods Lung adenocarcinoma cell line A549 was cultured and Taxol-resistant A549/Taxol cells were induced. The cells were divided into Smac peptide treatment group（ observation group） and Smac reverse peptide treatment group（ control group）. The proliferative activity of the cell,and expressions of intracellular apoptotic gene and resistance gene were recorded. In addition,the expression levels of apoptotic genes（ Livin,XIAP,Caspase-3,Caspase-7 and Caspase-9）,and those of intracellular drug-resistance genes（ mRNA of MDR,LRP,Topo-Ⅱ and GST-π） were measured. Results There were significant differences in cell proliferation activity at 12,18,and 24 hours after treatment in observation group and control group Twenty-four hours after treatment,mRNA expressions of Livin,XIAP,MDR,LRP,Topo-Ⅱ and GST-πwere significantly lower in observation group than in control group. Nevertheless,mRNA expressions of Caspase-3,Caspase-7 and Caspase-9 were significantly higher than those of the control group. Conclusion Smac peptide can improve the Taxol resistance of lung adenocarcinoma cells by down-regulating the expression of anti-apoptosis protein and drug resistance genes.