奥沙利铂诱导人小细胞肺癌NCI-H446细胞凋亡的研究

Antitumor effects of oxaliplatin on human small cell lung cancer NCI-H446 cells in vitro

目的:研究奥沙利铂对人肺癌细胞株NCI-H446生长抑制及诱导凋亡的作用并探讨其机制。方法:以不同浓度的奥沙利铂作用于NCI-H446细胞,应用采用噻唑蓝(MTT)法检测奥沙利铂对NCI-H446细胞生长的抑制作用。Hoechst33258荧光染色法观察细胞凋亡形态学变化;流式细胞术检测细胞周期和凋亡;分光光度法检测caspase-3、caspase-8、caspase-9的活性。结果:奥沙利铂可抑制NCI-H446细胞的生长并具有时间和剂量依赖性,Hoechst 33258荧光染色可见典型的细胞凋亡特征,流式细胞仪检测到细胞阻滞于S期和sub-G1峰。经过奥沙利铂诱导,caspase-3、caspase-9活性被上调,较对照组明显升高(P<0.05),caspase-8活性未见明显改变(P>0.05)。结论:奥沙利铂具有抑制肺癌细胞株NCI-H446增殖及诱导凋亡作用,此作用可能通过激活内源性凋亡途径实现。

Objective：To investigate the effects of oxaliplatin on the proliferation and apoptosis of human small cell lung cancer NCI-H446 cells and to study its mechanism.Methods：NCI-H446 cells were treated with different concentrations of oxaliplatin.The inhibition of NCI-H446 cells proliferation was estimated by MTT assay;Morphologic changes were observed using Hoechst33258;alteration of cell cycle and apoptosis were analyzed using flow cytometry;The activities of caspase-3,caspase-8 and caspase-9 were determined by spectrophotometry.Results：Oxaliplatin could inhibit the proliferation of NCI-H446 cells and the inhibition depended on the exposure time and dose.Marked morphological change of cell apoptosis was observed by Hoechst33258 staining;The analysis of cell cycle indicated that oxaliplatin blocked cells at S phase and sub-G1 cell peak.The activities of caspase-3 and caspase-9 were upregulated in the experimental group compared with the control group（P0.05）.On the other hand,the activity of caspase-8 was not significantly different between the experimental group and the control group（P0.05）.Conclusion：Oxaliplatin can effectively induce NCI-H446 cell apoptosis by activating the intrinsic apoptosis pathway.