中国中药杂志

2010, v.35(20) 2752-2755

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阿魏酸对人类乳腺癌细胞增殖作用机制的实验研究
Effect of ferulic acid on proliferation and mechanism in human breast cancer cells

郝庆秀;赵丕文;牛建昭;王继峰;于杰;薛晓鸥;
HAO Qingxiu 1,ZHAO Piwen2,NIU Jianzhao1,2,WANG Jifeng 2,YU Jie 2,XUE Xiaoou 2(1.Institute of Chinese Materia Medica,China Academy of Chinese Medicinal Sciences,Beijing 100700,China;2.Beijing University of Chinese Medicine,Beijing 100029,China)

摘要(Abstract):

目的:考察阿魏酸对人类乳腺癌细胞的增殖作用及可能的作用机制。方法:利用体外培养的ER阳性人乳腺癌细胞系T47D细胞和ER阴性人乳腺癌细胞系MDA-MB-231细胞,通过MTT增殖实验、流式细胞技术检测细胞周期分布、测定ER亚型蛋白表达和用实时荧光定量RT-PCR法检测阿魏酸对雌激素效应基因pS2的调控作用。结果:1×10-5~1×10-7mol.L-1的阿魏酸可促进T47D细胞增殖(P<0.05),1×10-8mol.L-1雌激素受体拮抗剂FaslodexTM能抑制这种增殖效应。实验浓度阿魏酸以及它们与1×10-8mol.L-1雌激素受体拮抗剂FaslodexTM共孵育对MDA-MB-231细胞的增殖作用无论在时效或者量效方面均无显著的统计学意义。阿魏酸能使T47D细胞S期细胞数增加,细胞分裂增殖指数升高(P<0.05);随着细胞的孵育时间延长至48 h,细胞分裂增殖指数与孵育24 h相比显著降低(P<0.01),实验浓度阿魏酸以及它们与1×10-8mol.L-1雌激素受体拮抗剂FaslodexTM共孵育使T47D细胞S期和G2M期细胞比例下降,G0-G1期比例升高,细胞周期停滞于G0-G1期。1×10-7,1×10-6mol.L-1阿魏酸可诱导T47D细胞ERα蛋白表达水平显著升高(P<0.01),而对ERβ蛋白表达水平无显著影响。1×10-7,1×10-6mol.L-1阿魏酸均上调T47D细胞雌激素依赖性基因pS2mRNA表达。结论:阿魏酸通过促进ER阳性乳腺癌细胞增殖、上调ERα蛋白和雌激素依赖性基因pS2mRNA表达水平,有植物雌激素样作用。
Objective: To investigate phytoestrogenic effects of ferulic acid in ER-positive T47D and ER-negative MDA-MB231 cells in culture.Method: T47D and MDA-MB231 human breast cancer cells were treated with ferulic acid and examined cell proliferation by means of MTT assay.Cell cycle distribution,ERα and ERβ expression were treated by flow cytometer.The pS2 mRNA expressions were detected by real-time fluorescence quantitative PCR.Result:The proliferations were enhanced significantly by treatment with ferulic acid on T47D cells and the proliferation effects were inhibited by adding FaslodexTM(1×10-8 mol·L-1).However,there was no significant difference on the proliferation in MDA-MB-231 cells compared with solvent control group by both treatment with ferulic acid and co-treatment with FaslodexTM(1×10-8 mol·L-1).Ferulic acid stimulated the amount of T47D cells in phase S and proliferation index increased significantly.The effects were inhibited by treatment with FaslodexTM(1×10-8 mol·L-1),and the amount of cells in phase S and proliferation index decreased,the amount of cells in G0/G1 phase increased,cell cycle of T47D was arrested in G0/G1 phase.Ferulic acid up-regulated pS2 mRNA expressions and increased the level of ERα protein expression in T47D cells.Ferulic acid did not show remarkable effect to the level of ERβ protein expression in T47D cells.Conclusion: Ferulic acid possessed phytoestrogenic effect by up-regulating pS2 gene expression and the receptor subtype of ERα.

关键词(KeyWords): 阿魏酸;T47D;MDA-MB-231;雌激素受体;pS2 mRNA
ferulic acid;T47D;MDA-MB-231;estrogen receptor;pS2 mRNA

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(30772849);; 国家科技支撑计划项目(2006BAI11B07);; 教育部长江学者和创新团队发展计划项目(IRT0413)

作者(Author): 郝庆秀;赵丕文;牛建昭;王继峰;于杰;薛晓鸥;
HAO Qingxiu 1,ZHAO Piwen2,NIU Jianzhao1,2,WANG Jifeng 2,YU Jie 2,XUE Xiaoou 2(1.Institute of Chinese Materia Medica,China Academy of Chinese Medicinal Sciences,Beijing 100700,China;2.Beijing University of Chinese Medicine,Beijing 100029,China)

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