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Effect of lidamycin on mitochondria initiated apoptotic pathway in human cancer cells
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- Author:
- No author available
- Journal Title:
- ACTA PHARMACEUTICA SINICA
- Issue:
- 2
- DOI:
- 10.3321/j.issn:0513-4870.2007.02.004
- Key Word:
- 力达霉素;线粒体;肿瘤;细胞凋亡
Abstract： 力达霉素(1idamycin,LDM)是具有我国自主知识产权的烯二炔类抗生素,具有较强的抗肿瘤活性,其抗肿瘤机制有待深入阐明.本研究主要利用人肝癌BEL-7402和乳腺癌MCF-7细胞研究了力达霉素对线粒体凋亡通路相关因子的影响.通过MTT法检测不同剂量力达霉素对肿瘤细胞增殖毒性;蛋白印迹技术检测线粒体和细胞质细胞色素c、总Bax,Bcl-2及p53表达;RT-PCR检测p53和bax mRNA表达等.结果发现,LDM能迅速激活肿瘤细胞线粒体凋亡通路,在2 h内就引起线粒体中细胞色素c释放至细胞质中.同时Bcl-2家族成员中促凋亡成员Bax持续增加,而抗凋亡成员Bcl-2先增加后减少.p53蛋白在6 h显著增加.Bax蛋白表达升高与其mRNA转录水平升高有关,p53蛋白表达升高与转录后水平有关.Caspase抑制剂可以部分抑制LDM的增殖毒性.因此LDM可以通过激活细胞色素c启动的线粒体凋亡通路发挥抗肿瘤作用.
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