吴茱萸碱诱导人子宫颈癌HeLa细胞凋亡的机制研究

目的研究吴茱萸碱(evodiamine)诱导人子宫颈癌HeLa细胞凋亡的分子生物学机制。方法用结晶紫法和琼脂糖凝胶电泳法以及用两种caspase的蛋白酶抑制剂测定细胞凋亡过程中caspase的信号传导路径。结果吴茱萸碱可诱导HeLa细胞的细胞膜皱缩、细胞质浓集及凋亡小体的形式,并清晰可见以180 bp倍数裂解的DNA梯形电泳带的出现。抑制剂VAD-fmk(caspase家族总抑制剂)和DEVD-fmk(caspase-3抑制剂)能部分抑制HeLa细胞的凋亡。结论Evodiamine诱导人宫颈癌HeLa细胞凋亡;caspase cascade信号传导路径与凋亡密切相关。

STUDIES ON EVODIAMINE INDUCED HELA CELL APOPTOSIS

AIM To study the mechanism of evodiamine induced growth inhibition of HeLa cells. METHODS HeLa cells viability and the effect of caspase inhibitors on evodiamine induced apoptosis were measured by crystal violet assay. Changes in cellular morphology were observed by phase contrast microscopy. Apoptosis specific nucleosomal DNA fragmentation was assayed by agarose gel electrophoresis. RESULTS Evodiamine was found to inhibit HeLa cell growth in dose and time dependent manners. Caspase 3 inhibitor, z Asp Glu Val Asp fmk (z DEVD fmk) was shown to partially inhibit evodiamine induced apoptosis. However, caspase 1 inhibitor, Ac Tyr Val Ala Asp chloromethyl ketone (Ac YVAD cmk), did not antagonize evodiamine induced cell death. CONCLUSION Evodiamine suppresses the growth of HeLa cells in vitro by apoptosis. Evodiamine induced apoptosis is partially dependent on caspase 3 pathway in HeLa cells. Other apoptotic pathways might be also related to the induction of apoptosis by evodiamine.