摘要
目的在确定哇巴因是否经雌激素受体(estrogen re-ceptor,ER)途径发挥抗乳腺癌细胞增殖作用的基础上,进一步探讨ER亚型在哇巴因介导的增殖抑制中的作用。方法选择兼有两种ER亚型表达的人乳腺癌细胞株MCF-7为研究对象,采用MTT法、RNA干扰技术及蛋白印迹检测技术,观察ER亚型对哇巴因介导的细胞增殖抑制作用的影响。结果在0.1～1 000 nmol.L-1浓度范围内,哇巴因以剂量依赖性方式明显抑制MCF-7细胞的增殖活性,该抑制作用可被ER阻断剂ICI 182,780部分阻断。应用RNA干扰技术沉默ERα或ERβ基因表达,进一步证实哇巴因对MCF-7细胞的增殖抑制作用主要由ERα介导。结论哇巴因可通过ERα信号通路对乳腺癌发挥抗肿瘤效应。NKA结合ER可能是未来开发抗乳癌药物的潜在重要靶点。
Aim To explore whether ouabain has an inhibitory effect on cell proliferation of breast cancer.Methods Based on our previous studies,human breast cancer MCF-7 cell line containing two ER isoforms was a suitable model for this study.MTT assay,RNA interfering（RNAi） technology and Western blot were performed to investigate the role of ER isoforms in the inhibitory activity of ouabain.Results Ouabain could inhibit cell proliferation in a dose-dependent manner from 0.1 to 1 000 nmol.L-1.Treatment with the ER antagonist ICI 182,780 abrogated the above actions partly.The use of RNAi technology further demonstrated that the effects of ouabain on cell proliferation were mainly mediated by ERα.Conclusion Ouabain can exhibit an anti-tumor activity in breast cancer via ERα pathway principally.NKA in combination with ERs can be potentially important targets for developing the anti-breast cancer drugs.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2012年第12期1694-1698,共5页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81273552
30901985)
