关键词: 哺乳动物雷帕霉素靶蛋白, 磷脂酰肌醇3-激酶, 柯萨奇病毒B 3, 细胞凋亡

Abstract: Objective To observe the effect of the inhibitor of mTOR (mammalian target of rapamycin) Rapamycin and the inhibitor of PI3K (phosphatidylinositol kinase 3-kinase) LY294002 on Bim and Bax---members of pro-apoptosis factors in Bcl-2 family in CVB3 (coxsackievirus B3) induced HeLa cells, further investigate the roles of PI3K and mTOR signaling pathway playing in the CVB3 induced apoptosis. Methods To construct a cell model of VMC (viral myocarditis) with subculture HeLa cells. HeLa cells infected by CVB3 were treated with 10 nM Rapamycin and 25 μM LY294002 according to the cell toxicity test. The Bim and Bax expressions were determined by both RT-PCR and Western blot. Results Compared with controls (CVB3+DMSO), CPE (cytopathic effect) at 3h and 6h pi (postinfection) were no significant difference which at 12h and 24h pi, however, CPE in LY294002 and Rapamycin group were more obviously. Compared with Sham, the mRNA and protein expression of Bim decreased induced by CVB3 which blocked by LY294002 and Rapamycin compared with controls. The mRNA expression of Bax decreased early after CVB3 infection while protein expression increased gradually, which was dynamically affected by LY294002 and Rapamycin. Conclusion LY294002 and Rapamycin promote HeLa cells apoptosis and expression of both Bim and Bax with the infection time, which illustrates that PI3K and mTOR signaling pathway may play important roles in CVB3 induced VMC by regulating the Bim and Bax expressions.

Key words: mammalian target of rapamycin, phosphatidylinositol kinase 3-kinase, coxsackievirus B3, apoptosis