他莫昔芬通过容积激活性氯电流抑制肝癌细胞增殖.docVIP

他莫昔芬通过容积激活性氯电流抑制肝癌细胞增殖[摘要] 目的:探讨他莫昔芬(TAM)对人肝癌SMMC 7721细胞增殖的影响以及与容积激活性氯电流的关系。方法:MTT法检测TAM对细胞增殖的作用;流式细胞术检测TAM对细胞周期的影响;全细胞膜片钳技术观察TAM对容积激活性氯电流的抑制作用。结果:TAM能浓度依赖性地抑制SMMC 7721细胞的增殖和低渗激活的容积激活性氯电流,两者呈正向直线相关;TAM也阻滞细胞周期于G0/G1期。结论:TAM通过调节容积激活性氯通道的开放抑制SMMC 7721细胞的增殖,容积激活性氯通道可能是TAM抗肿瘤特别是雌激素受体阴性肿瘤的靶点。 [关键词] 肝癌;他莫昔芬;细胞增殖;氯通道 [中图分类号] R963[文献标识码]A [文章编号]1673-7210(2009)07(a)-039-03 Effects of Tamoxifen on proliferation and volume-activated chloride current in human hepatocellular carcinoma cells MAO Jianwen1, XU Bin2, WANG Weizhang1, YUAN Jian1, CHEN Weiqiang1, LI Hongzhi1 (1.School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou 510006,China;2. School of Life Science and Biopharmacology, Guangdong Pharmaceutical University, Guangzhou 510006, China) [Abstract] Objective: To investigate the role of the volume-activated chloride current (Icl,vol) on inhibition effects of tamoxifen on the proliferation in human hepatocellular carcinoma cells SMMC 7721. Methods: MTT assay was used to determine the inhibition of TAM on cell proliferation. The whole cell patch clamp technique was used to observe the effects of tamoxifen on Icl,vol. Results: Tamoxifen inhibited the cell proliferation, Icl,vol in a concentration-dependent manner and arrested cell cycle on G0/G1 phase. Analysis of the relationships between the current and cell proliferation showed that the current was positively correlated with cell proliferation. Conclusion: These data indicate that tamoxifen may inhibit cell proliferation by modulating Icl,vol. The Icl,vol may be an extra-estrogen receptor site of action for tamoxifen and may account, in part, for its anti-growth effects on estrogen receptor-negative cancers. [Key words] Hepatocellular carcinoma; Tamoxifen; Cell proliferation; Chloride channels 他莫昔芬(tamoxifen,TAM) 又称三苯氧胺,是一种非甾体类抗雌激素药物。目前广泛应用于雌激素受体阳性的乳腺癌和卵巢癌的临床治疗[1]。但研究发现TAM也对雌激素受体阴性的某些肿瘤(如肝癌[2]、肺癌[3]和前列腺癌[4])有治疗作用,其机制尚未阐明。近年研究发现TAM也是容积激活性氯电流抑制剂[5-6],能有效阻抑容积激活性氯通道的开放,而后者在肿瘤细胞生长中扮演了重要的角