赖氨大黄酸与顺铂联合对人肺癌A549细胞系增殖和凋亡的影响  

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

作　　者：纪春梅 甄永占[2] 范晓禹[3] 王志军 蒋守芳[5] 朱丽华[2] 章广玲[2] 

机构地区：[1]河北唐山协和医院呼吸内科 [2]河北联合大学基础医学院组织学与胚胎学教研室 [3]开滦医疗集团林西医院呼吸内科,河北唐山063000 [4]河北唐山丰润区第二人民医院放射科,河北唐山064000 [5]河北联合大学公共卫生学院职业与环境卫生科,河北唐山063000

出　　处：《基础医学与临床》2014年第2期155-159,共5页Basic and Clinical Medicine

基　　金：国家自然科学基金(81001439);河北省自然科学基金(H2012401030);唐山市科学技术研究与发展资助项目(131302101z)

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。方法肺癌细胞系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48 h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。Objective To investigate the effect of Rhein lysinate （RHL）, cisplatin and their combination on the proliferation and apoptosis of lung cancer A549 cells, and to provide theoretical support to cisplatin combined with RHL against human lung cancer. Methods The lung cancer A549 cells in logarithm growth phase were selected and then randomly divided into four groups： blank control group, cisplatin group, RHL group and combination groups.MTI＂ assay was used to detect A549 cell proliferation and flow cytometry was used to analyze cell apoptosis in vari- ous groups after 48 h. The expression 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 cis- platin 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 ）. The expression of cleaved caspase-3, caspase-7 and poly ADP-ribose polymerase （PARP） in combination group was higher than those from 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 downregulated the phosphorylation of ERK induced by cisplatin. Conclusions RHL enhanced cisplatin-induced cytotoxicity and apoptosis by reducing the activation of ERK and increasing the level of cleaved caspase-3, caspase-3 and PARP.

关 键 词：赖氨大黄酸 顺铂 肺癌 细胞凋亡 联合用药 

分 类 号：R734.2[医药卫生—肿瘤]