赖氨大黄酸抑制HER2信号通路对肺癌H460细胞的凋亡诱导作用  

Apoptotic induction effect of rhein lysinate in lung cancer H460 cells by inhibiting HER2 signal pathway

作　　者：甄永占[1] 纪春梅[2] 赵毓芳[1] 闫丰[3] 刘志勇[3] 朱丽华[1] 林雅军[4] 

机构地区：[1]河北联合大学基础医学院组织学与胚胎学教研室,河北唐山063000 [2]河北省唐山市协和医院呼吸内科,河北唐山063000 [3]河北联合大学附属医院肿瘤科,河北唐山063000 [4]卫生部北京医院北京老年医学研究所,北京100730

出　　处：《吉林大学学报（医学版）》2013年第4期661-666,共6页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金资助课题(81001439);河北省科技厅自然科学基金资助课题(H2012401030)

摘　　要：目的:研究赖氨大黄酸(RHL)对肺癌H460细胞增殖、凋亡的影响及人类表皮生长因子受体2(HER2)信号通路在其中的作用,为RHL抗肺癌的临床实验研究提供依据。方法:选取HER2高表达并处于对数生长期的H460细胞,随机分为空白对照组和25、50、75、100、125、150μmol.L-1 RHL组,采用MTT法检测各组细胞增殖活性。H460细胞随机分为空白对照组及50、100、150μmol.L-1 RHL组,流式细胞术检测各组细胞48h凋亡情况,Western blotting法检测各组细胞48h后凋亡相关蛋白和HER2信号通路蛋白的表达。结果:细胞培养48h后,不同浓度RHL组H460细胞存活率显著低于空白对照组(P<0.05),细胞凋亡率显著高于空白对照组(P<0.05),RHL的增殖抑制作用和凋亡诱导作用呈剂量依赖性。不同浓度RHL组H460细胞Caspase-3、Caspase-7和聚腺苷酸二磷酸核糖转移酶(PARP)的切割片段蛋白表达明显高于空白对照组(P<0.05),HER2、AKT蛋白磷酸化水平和NF-κB蛋白的表达水平明显低于空白对照组(P<0.05)。结论:RHL可能通过抑制HER2/AKT/NF-κB信号通路诱导H460细胞凋亡。Objective To investigate the effect of rhein lysinate（RHL）on the proliferation and apoptosis of human lung cancer cell line H460and the role of human epidermal growth factor receptor-2（HER2）signal pathway in apoptosis,and to provide theoretical foundation for clinical research on RHL against lung cancer.Methods The H460cells in which HER2was over-expressed in logarithm growth phase were selected and randomly divided into blank control group and different concentrations（25,50,75,100,125,and 150μmol.L-1）of RHL groups.MTT assay was used to detect the proliferation abilities of H460cells in various groups.The H460cells were randomly divided into blank control group and 50,100,and 150μmol.L-1 RHL groups;flow cytometry was used to analyze apoptosis in various groups after 48h.The expression levels of apoptosis-related proteins and HER2 signal pathway proteins were detected after 48hby Western blotting method.Results After 48hcell culture,the cell viability rates in RHL groups were lower than that in blank control group（P0.05）,whereas the apoptotic rates in RHL groups were higher than that in blank control group（P0.05）.The inhibition of cell proliferation of RHL presented a dose-dependent manner in H460cells,and so the apoptosis induced by RHL.The expressions of cleaved poly ADP-ribose polymerase（PARP）and caspase-3/7in RHL groups were higher than those in blank control group（P0.05）after 48hcell culture in H460cells,whereas the expressions of phosphorylation of HER2 and AKT and NF-κB were lower than those in control group（P0.05）.Conclusion RHL can induce apoptosis by inhibiting HER2/AKT/NF-κB signal pathway in H460cells.

关 键 词：赖氨大黄酸 肺肿瘤 细胞凋亡 HER2信号通路 

分 类 号：R734.2[医药卫生—肿瘤]