基础医学与临床 ›› 2011, Vol. 31 ›› Issue (1): 68-72.

• 研究论文 • 上一篇    下一篇

赖氨大黄酸通过激活JNK诱导宫颈癌HeLa细胞凋亡

甄永占1,林雅军2,骆广玲3,赵毓芳1,高俊玲1   

  1. 1. 华北煤炭医学院2. 卫生部北京医院3. 开滦医疗集团林西医院
  • 收稿日期:2010-06-23 修回日期:2010-07-30 出版日期:2011-01-05 发布日期:2011-01-05
  • 通讯作者: 高俊玲

Rhein lysinate induces apoptosis in human cervical cancer HeLa cells by activating c-Jun NH2-terminal kinase (JNK)

ZHEN Yong-zhan 1,LIN Ya-jun 2,LUO Guang-ling 2,ZHAO Yu-fang 2,GAO Jun-ling 3   

  1. 1. North China Coal Medical University2. 3. North China Coal Medical Univesrity
  • Received:2010-06-23 Revised:2010-07-30 Online:2011-01-05 Published:2011-01-05
  • Contact: GAO Jun-ling

摘要: 目的:研究赖氨大黄酸 (RHL)对人宫颈癌HeLa细胞增殖、凋亡的影响,并探讨其作用机理。方法:用MTT法检测细胞增殖;用流式细胞仪检测细胞凋亡,用Western blot 检测凋亡相关蛋白及JNK蛋白与蛋白磷酸化水平。结果:RHL 能有效抑制宫颈癌HeLa细胞增殖,并能诱导其凋亡,随药物浓度的增加,细胞凋亡率也逐渐升高;RHL能够激活Caspase-3、Caspase-7和PARP,并激活磷酸化的JNK表达,磷酸化的JNK表达增加在RHL的诱导凋亡中起主要作用。结论:RHL通过激活JNK-Caspase-PARP信号通路抑制HeLa细胞增殖,并诱导其凋亡,赖氨大黄酸解决了大黄酸不溶于水的问题,有望成为临床肿瘤辅助化疗药物。

关键词: 赖氨大黄酸, 细胞凋亡, 宫颈癌, JNK

Abstract: Objective: This study is to investigate the effect of Rhein lysinate (RHL) on inducing human cervical cancer cell line HeLa apoptosis and the role of activation of c-Jun NH2-terminal kinase (JNK) in cell apoptosis. Methods: MTT assay was used to detect HeLa cell proliferation. Cell apoptosis was analyzed by flow cytometry. The protein associated with apoptosis and the protein phosphorylation of JNK were detected by Western blot. Results: RHL remarkably inhibited cervical cancer HeLa cells proliferation. The IC50 value for 48 h and 72 h treatment was 81.18 μmol/L and 72.38 μmol/L respectively. Apoptosis in HeLa cells was induced by RHL in a dose dependent manner. Mechanistically, RHL triggered HeLa cells apoptosis by increasing the levels of cleaved poly ADP-ribose polymerase (PARP) and caspase-3/7. In addition, activation c-Jun NH2-terminal kinase (JNK) was a critical mediator in RHL-induced growth inhibition. Inhibition of the phosphorylation of JNK by pharmacological inhibitors reversed the RHL-induced growth inhibition through decreasing the level of cleaved PARP and caspase-3/7. Conclusion: RHL suppresses HeLa cells growth and induce apoptosis through the activation of JNK-Caspase-PARP signal pathway, with the potential to be developed as a chemotherapeutic agent for cervical cancer.