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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2009, Vol. 29 Issue (04): 35-38    
研究报告     
Mcl-1在胆盐(GCDA)诱导的肝癌细胞耐药中的作用
廖明媚1,张阳德1,段菁华1,何剪太1,潘一峰1,邓星明1,2,赵劲风1
1. 中南大学卫生部肝胆肠外科研究中心
2. Shands Cancer Center and Department of Medicine, University of Florida, Gainesville
Role of Mcl-1 in Bile Salt (GCDA)-induced Chemoresistance of Hepatocellular Carcinoma Cells
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摘要:

目的:探讨抗凋亡蛋白Mcl-1在GCDA诱导的肝癌细胞耐药中的作用及其机制。方法:培养3种肝癌细胞系,用免疫荧光法和Western blot技术检测Mcl-1的表达;GCDA±CYC处理HepG2细胞,采用Western blot技术检测Mcl-1的半衰期变化;用抗癌药物Irinotecan与GCDA对HepG2细胞进行处理,采用MTT法和Western blot技术分别检测细胞增殖抑制率和Mcl-1的表达变化;用RNA干扰技术下调Mcl-1,检测化疗药物对HepG2细胞的敏感性。结果:Mcl-1在肝癌细胞中广泛表达;GCDA能延长Mcl-1的半衰期至6h以上,并明显减弱化疗药物对抗凋亡蛋白Mcl-1的抑制作用,降低癌细胞的药物敏感性;RNA干扰下调Mcl-1能增加癌细胞的药物敏感性。结论:胆盐(GCDA)能诱导HepG2细胞产生耐药性,其作用机制可能是通过延长Mcl-1半衰期增加其蛋白稳定性和抗凋亡作用来促使肝癌细胞抗药的。

Abstract:

Objective: To study the role of anti-apoptotic protein Mcl-1 in bile salt (GCDA)-induced chemoresistance of hepatocellular carcinoma cells. Methods: Three HCC cell lines were cultured in CO2 incubator. Expression of Mcl-1 was analyzed by immunofluorescence and Western blot. HepG2 cells were treated by GCDA±CYC or Irinotecan±GCDA. Protein expression and cell viability were assessed by Western blot and MTT, respectively. Drug sensitivity was detected after down-regulation of Mcl-1 by RNA interference in HepG2 cells.Results: Mcl-1 protein is extensively expressed in HCC cells. GCDA prolongs half-life of Mcl-1 from 2-3h to more than 6h and reduces inhibitory action of Irinotecan to Mcl-1. Down-regulation of Mcl-1 by RNA interference can enhance drug sensitivity of HepG2 cells. Conclusion: Bile salt (GCDA) can induce chemoresistance of HepG2 cells. This occurs by increasing protein stability and anti-apoptotic activity of Mcl-1.

收稿日期: 2008-09-08 出版日期: 2009-04-27
基金资助:

湖南省芙蓉学者计划课题(200734)资助项目

通讯作者: 赵劲风   
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廖明媚 张阳德 段菁华 何剪太 潘一峰 邓星明 赵劲风

引用本文:

廖明媚,张阳德,段菁华,何剪太,潘一峰,邓星明,赵劲风. Mcl-1在胆盐(GCDA)诱导的肝癌细胞耐药中的作用[J]. 中国生物工程杂志, 2009, 29(04): 35-38.

LIAO Meng-Mei- Zhang-Yang-De- Duan-Jing-Hua- He-Jian-Ta- Bo-Yi-Feng- Deng-Xing-Meng- Diao-Jin-Feng. Role of Mcl-1 in Bile Salt (GCDA)-induced Chemoresistance of Hepatocellular Carcinoma Cells. China Biotechnology, 2009, 29(04): 35-38.

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https://manu60.magtech.com.cn/biotech/CN/        https://manu60.magtech.com.cn/biotech/CN/Y2009/V29/I04/35

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