顺铂诱导人小细胞肺癌细胞系NCI-H446细胞的凋亡

Apoptosis induced by DDP in human SCLC cell line NCI-H446 cells

背景与目的：近年的研究表明,诱导细胞凋亡是多种作用于核酸代谢不同环节的化疗药物抗肿瘤的重要机制.但顺铂杀灭人小细胞肺癌（SCLC）细胞的药物效应除了损伤其DNA外,诱导该类恶性肿瘤细胞凋亡是否是其杀灭细胞的重要机制尚无相应研究.基于此,本研究旨在探讨顺铂诱导人SCLC细胞系H446细胞凋亡的机制及其在SCLC化疗中的作用.方法：分别采用形态学观察、流式细胞仪分析技术和原位DNA断裂点的末端标记法,检测顺铂诱导H446细胞的凋亡作用.结果：终浓度分别为0.1、0.5、1.0、2.0、5.0 μg/ml的顺铂均可诱导H446细胞凋亡,且呈浓度依赖性（处理48 h时,其凋亡指数分别为1.47±0.03、8.28±0.54、11.02±1.05、12.74±1.08、27.16±1.15）;终浓度为2 μg/ml的顺铂在24～72 h持续诱导细胞凋亡且诱导凋亡作用逐渐增强,呈时间依赖性;终浓度为5 μg/ml的顺铂可阻滞H446细胞于细胞周期的S期,终浓度＜5 μg/ml顺铂可阻滞H446细胞于细胞周期的G2期和S期.结论：诱导细胞凋亡可能是顺铂抗肿瘤作用的重要机制.

Background and purpose： Recent studies show that apoptosis induced by chemotherapeutic drugs may be involved in the different steps of nuclear metabolism. Whether small cell lung cancer（SCLC） cells apoptosis induced by cisplatin（DDP） associated with the same molecular mechanism is still under investigation. The purpose of our study was to discover the mechanism of human SCLC cell line H446 cell apoptosis induced by DDP. Methods： Apoptosis induced by DDP in human SCLC cell line H446 was detected by cell morphology, flow cytometry analysis and DNA end labeling, respectively. Results： H446 cells were treated with the concentrations of 0.1, 0.5, 1.0, 2.0 and 5.0 μg/ml DDP for 48 hr, respectively. Apoptotic index were 1.47±0.03, 8.28±0.54, 11.02±1.05, 12.74±1.08, 27.16±1.15, respectively and apoptosis was induced in both a concentration dependent manner and gradually in a time dependent pattern from 12 to 72 hr with a final concentration of 2.0 μg/ml; H446 cells were blocked either at G2 by the final concentration of 0. 1, 0. 5, 1.0 and 2.0 μg/ml DDP or at S phase with the final concentration of 5.0 μg/ml DDP. Conclusions： Cell apoptosis induced by DDP may play an important role in the mechanism of DDP antitumor effect.