目的：研究减毒水泡性口炎病毒（vesicular stomatitis virus，VSV）对宫颈癌HeLa细胞的凋亡诱导作用，并探讨其可能的机制。方法：将减毒VSV以1.0 MOI的接种密度感染HeLa细胞，在6、12、18、24和30 h后收集细胞，MTT法检测HeLa细胞的增殖；AO/EB染色观察HeLa细胞凋亡形态学变化，Annexin V-FITC/PI双染法检测HeLa细胞早期凋亡率，流式细胞术分析HeLa细胞sub-G1凋亡峰，JC-1染色法测定细胞线粒体跨膜电位水平，caspase试剂盒检测HeLa细胞caspase-3、caspase-8及caspase-9的活性。结果：减毒VSV感染HeLa细胞12和24 h后，HeLa细胞增殖活力分别为（78.4±1.9）% 和（63.1±56）%（P<0.01）；早期凋亡细胞率分别为（16.88±2.48）%和（31.9±4.24）%（P<0.01），sub-G1凋亡峰分别为（14.85±148）% 和（21.05±2.28）%（P<0.01）。随着减毒VSV感染时间的增加，HeLa细胞线粒体跨膜电位逐渐降低（P<0.05），caspase-9和caspase-3的活性显著升高（均P<0.05）。结论：减毒VSV能够抑制HeLa细胞的增殖，并通过caspase-9和caspase-3依赖的途径诱导HeLa细胞凋亡。

Objective:To investigate the apoptosis-inducing effect of an attenuated vesicular stomatitis virus in cervical cancer HeLa cells, and to explore the possible mechanism. Methods: HeLa cells were infected with VSV (MOI=1.0) and the cell proliferation was determined by MTT assay at 6, 12, 18, 24, and 30 h after infection. Morphological changes of apoptosis were observed by acridine orange (AO)/ethidium bromide (EB) staining. Annexin V/PI double-staining was performed to detect early apoptosis rate of HeLa cells and the sub-G1 apoptotic peak was examined by flow cytometry. The mitochondrial membrane potential of HeLa cells was measured by the JC-1 staining. The activities of caspase-9, -8 and -3 were measured by caspase assay kit. Results: After HeLa cells were exposed to attenuated VSV for 12 h and 24 h, the viabilities of cells were reduced to (78.4±1.9)% and (63.1±5.6)% (P<0.01); the early apoptosis rates were (16.88±248)% and (31.9±4.24)% (P<0.01); the Sub-G1 apoptotic peaks were (14.85±1.48)% and (21.05±228)% (P<0.01), respectively. Attenuated VSV significantly decreased mitochondrial membrane potential in HeLa cells with the increase of infection time (P<0.05). The activities of caspase-9 and caspase-3 of HeLa cells were significantly increased after VSV infection (all P<0.05). Conclusion: The attenuated VSV can inhibit the proliferation of HeLa cells and trigger apoptosis via caspase-9 and caspase-3-dependent pathway.

国家自然科学基金资助项目（No. 31001070）；吉林省科技发展计划项目（No. 20100146）；军事医学科学院第十一研究所创新启动基金资助项目(No.YCX0902)