吉林大学学报(医学版)

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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

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   

  1. (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)
  • 收稿日期:2012-12-19 出版日期:2013-07-28 发布日期:2013-08-07
  • 通讯作者: 林雅军 E-mail:(Tel: 010-58115040,E-mail: linyajun2000@126.com)
  • 作者简介:甄永占(1970-),女,河北省唐山市人,副教授,医学博士,主要从事肿瘤分子药理学研究。
  • 基金资助:

    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)

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

ZHEN Yong-zhan1,JI Chun-mei2,ZHAO Yu-fang1,YAN Feng3,LIU Zhi-yong3,ZHU Li-hua1,LIN Ya-jun4#br#    

  1. (1.Department of Histology and Embryology,College of Basic Medical Sciences,Hebei United University,Tangshan 063000,China; 2. Department of Respiratory Medicine,Xiehe Hospital,TangshanCity,Hebei Province,Tangshan 063000,China; 3. Department of Oncology,Affiliated Hospital,Hebei United University, Tangshan 063000,China; 4. Beijing Hospital,Beijing Institute of Geriatrics,Ministry of Health,Beijing 100730,China)
  • Received:2012-12-19 Online:2013-07-28 Published:2013-08-07

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抗肺癌的临床试验研究提供依据。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、150  μmol•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、150  μmol•L-1 RHL组,流式细胞术检测各组细胞48 h凋亡情况,Western blotting法检测各组细胞48 h后凋亡相关蛋白和HER2信号通路蛋白的表达。结果: 细胞培养48 h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。

关键词: 赖氨大黄酸, 肺肿瘤, 细胞凋亡, HER2信号通路

Abstract:

Abstract:Objective
To investigate the effect of rhein lysinate (RHL) on the proliferation and apoptosis of human lung cancer cell line H460 and 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 H460 cells in which HER2 was over-expressed in logarithm growth phase were selected and randomly divided into blank control group and different concentrations (25,50,75,100,125,and 150 μmol•L-1) of RHL groups. MTT assay was used to detect the proliferation abilities of H460 cells in various groups. The H460 cells were randomly divided into blank control group and 50,100,and 150 μmol•L-1 RHL groups; flow cytometry was used to analyze apoptosis in various groups after 48 h. The expression levels of  apoptosis-related proteins and   HER2 signal pathway proteins were detected after 48 h by Western blotting method. Results  After 48 h cell culture,the cell viability rates in RHL groups were lower than that in blank control group (P<0.05),whereas the apoptotic rates in RHL groups were higher than that in blank control group (P<0.05). The inhibition of cell proliferation of RHL presented a dose-dependent manner in H460 cells,and so the apoptosis induced by RHL. The expressions of cleaved poly ADP-ribose polymerase (PARP) and caspase-3/7 in RHL groups were higher than those in blank control group (P<0.05) after 48 h cell culture in H460 cells,whereas the expressions of phosphorylation of HER2 and AKT and NF-κB were lower than those in control group (P<0.05).Conclusion RHL can induce apoptosis by inhibiting HER2/AKT/NF-κB signal pathway in H460 cells.

Key words: rhein lysinate, lung neoplasms, apoptosis, HER2 signal pathway

中图分类号: 

  • R734.2