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Fascaplysin通过诱导细胞凋亡抑制HeLa细胞体外增殖 被引量:9

Anti-proliferation of human cervical cancer HeLa cell line by fascaplysin through apoptosis induction
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摘要 观察fascaplysin对人宫颈癌HeLa细胞体外增殖的抑制作用及其分子机制。MTT法显示fascaplysin对HeLa细胞体外增殖有显著的抑制作用,其IC50为1.79μmol·L-1;流式细胞周期检测显示,fascaplysin未能诱导HeLa细胞发生G1期阻滞,但出现浓度依赖性的sub-G1期峰;Annexin V/PI染色证实fascaplysin能诱导HeLa细胞发生凋亡,且以早期凋亡为主;Western blotting分析显示,fascaplysin能下调CDK4和cyclin D1的蛋白表达,并引起CDK4/cyclinD1特异性pRb位点Ser795的蛋白磷酸化水平下降;caspase-3、-9活性检测以及Western blotting结果证明,fascaplysin能显著增加活性caspase-3、-9的水平,下调pro-caspase-8的蛋白表达,使Bid表达减少,促进胞浆中细胞色素c释放增多,同时还能下调Bcl-2的蛋白表达。研究结果表明,fascaplysin虽然抑制了CDK4/cyclin D1复合物的活性,但并未能使HeLa细胞阻滞于G1期。该化合物对HeLa细胞体外增殖的抑制作用是通过剂量依赖性地诱导细胞凋亡实现的,其机制可能与激活caspase-8前体的活性,Bid切割为tBid数量的增加,抑凋亡因子Bcl-2表达的下调,胞浆中细胞色素c含量的增多,以及活性caspase-3、-9水平的增加有关。 This study is to investigate the effect of fascaplysin on human cervical cancer cells (HeLa) in order to provide insights into the mechanisms of growth suppression involved in fascaplysin-mediated apoptosis. Cytotoxic activity of fascaplysin on HeLa cells was determined using MTT assay, cell cycle analysis, and apoptosis (Annexin V-FITC and PI double staining) studies. The role of the molecules in cell cycle regulation and apoptosis was analyzed by Western blotting and flow cytometry. Fascaplysin markedly inhibited HeLa cells proliferation in a dose-dependent manner, however, did not provoke Gt phase arrest in HeLa cells with down- regulation of CDK4, cyclin D1 and CDK4-specific Ser795 pRb phosphorylation. Furthermore, fascaplysin induced significantly apoptosis evidenced by sub-G1 peak and Annexin V-FITC and PI double staining. The molecular mechanism of fascaplysin-induced apoptosis was characterized with the activation of caspase-3, -8, and -9, truncation of Bid, release of cytochrome c into cytosol, and down-regulation of Bcl-2 level. Fascaplysin exhibits anti-proliferation effect towards human cervical cancer HeLa cells through induction of apoptosis via extrinsic death pathway and mitochondrial pathway, but not arresting cell cycle progression at Gt phase. All together, these data sustain our contention that fascaplysin has anticancer properties and merits further investigation as a potential therapeutic agent.
出处 《药学学报》 CAS CSCD 北大核心 2009年第9期980-986,共7页 Acta Pharmaceutica Sinica
基金 国家高新技术研究发展计划(863计划)资助项目(2007AA09Z412) 宁波大学王宽诚幸福基金 长江学者和创新团队发展计划资助项目(IRT0734)
关键词 fascaplysin CDK4 细胞凋亡 caspases活化 线粒体 fascaplysin CDK4 apoptosis caspases activation mitochondria
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参考文献19

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  • 1CUI ShiHai1,2, YANG Jing1, LIU ShuShen2,3 & WANG LianSheng2 1 College of Chemistry and Environment, Nanjing Normal University, Nanjing 210097, China,2 State Key Laboratory of Pollution Control and Resources Reuse, School of the Environment, Nanjing University, Nanjing 210093, China,3 Key Laboratory of Yangtze Aquatic Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.Predicting bioconcentration factor values of organic pollutants based on medv descriptors derived QSARs[J].Science China Chemistry,2007,50(5):587-592. 被引量:7
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