基础医学与临床 ›› 2014, Vol. 34 ›› Issue (2): 155-159.

• 研究论文 • 上一篇    下一篇

赖氨大黄酸与顺铂联合对人肺癌A549细胞株增殖和凋亡的影响

纪春梅1,甄永占2,范晓禹3,王志军4,蒋守芳5,朱丽华2,章广玲6   

  1. 1. 河北唐山协和医院呼吸内科,河北 唐山
    2. 河北联合大学 基础医学院
    3. 开滦医疗集团 林西医院
    4. 河北唐山丰润区第二人民医院
    5. 河北联合大学 公共卫生学院
    6. 河北联合大学基础医学院
  • 收稿日期:2013-08-05 修回日期:2013-11-05 出版日期:2014-02-05 发布日期:2014-01-13
  • 通讯作者: 甄永占 E-mail:yongzhanzhen3333@sina.cn
  • 基金资助:
    赖氨大黄酸延缓血管内皮细胞衰老的作用及机制研究;力达霉素及其联合bortezomib抗多发性骨髓瘤作用机制研究

Effects of rhein lysinate and cisplatin on proliferation inhibition and apoptosis inducing of lung cancer A549 cells

  • Received:2013-08-05 Revised:2013-11-05 Online:2014-02-05 Published:2014-01-13

摘要: 目的 研究赖氨大黄酸(RHL)、顺铂和两者联合对人肺癌A549细胞增殖和凋亡的影响及其作用机制,为RHL联合顺铂抗肺癌的临床实验研究提供理论依据。方法 肺癌细胞株A549随机分为对照组、顺铂组、RHL组和顺铂联合RHL组,用MTT法和流式细胞术分别检测细胞48 h增殖和凋亡。Western blot 法检测细胞48h后凋亡相关蛋白和MEK/ERK蛋白的表达。结果 细胞培养48 h后,顺铂组和RHL组的细胞增殖受到一定的抑制并有细胞凋亡发生,但两药联合后的增殖抑制作用和凋亡诱导作用显著高于单用顺铂和RHL组(P<0.05)。顺铂和RHL均能上调caspase-3、caspase-7和poly ADP-ribose polymerase (PARP)的切割片断蛋白表达,但两药联合后caspase-3、caspase-7和PARP的切割片断蛋白表达进一步增高(P<0.05),并显著下调Bcl-2蛋白的表达水平,上调Bax蛋白的表达水平,同时RHL还能降低顺铂上调的ERK蛋白磷酸化。结论 RHL能够通过抑制顺铂对ERK的激活、上调caspase-3、caspase-7和PARP的切割片断蛋白表达,增强顺铂对肺癌细胞增殖和凋亡诱导作用。

关键词: 赖氨大黄酸, 顺铂, 肺癌, 细胞凋亡, 联合用药

Abstract: Objective To investigate the effect of Rhein lysinate (RHL), cisplatin and their combination on the proliferation, apoptosis of lung cancer A549 cells, and to provide theoretical foundation for cisplatin combined with RHL against human lung cancer. Methods The lung cancer A549 cells in logarithm growth phase were selected as the research object, and were randomly divided into four groups: blank control group, cisplatin group, RHL group and combination groups. MTT assay was used to detect A549 cell proliferation and flow cytometry was used to analyze cell apoptosis in various groups after 48 h. The expression levels of protein associated with apoptosis and protein of ERK were detected after 48 h by Western blotting. Results Cell proliferation was inhibited and cell apoptosis was induced in groups of cisplatin and RHL, but there was a significant reduction in proliferation and a significant increase in apoptosis in A549 cells treated with a combination of cisplatin and RHL compared with cisplatin or RHL treatment alone (P<0.05, respectively). The expressions of cleaved caspase-3, caspase-7 and poly ADP-ribose polymerase (PARP) in combination groups were higher than those of either agent alone group after 48 h cell culture in A549 cells, whereas the expression of BCL-2 was lower than those of either agent alone group and the expressions of BAX was higher than those of either agent alone group. Moreover, RHL could downregulate the phosphorylation of ERK induced by cisplatin. Conclusion RHL potentiates the cisplatin-induced cytotoxicity and apoptosis by reducing the activation of ERK and increasing the levels of cleaved caspase-3, caspase-3 and PARP.

Key words: rhein lysinate, Cisplatin, lung cancer, apoptosis, combination therapy

中图分类号: