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2月14日，BJC在线发表了法国研究人员的研究论文，他们发现联合使用他汀类药物和紫杉醇可有效引发癌细胞凋亡。 他汀类是一种主要的治疗高胆固醇血症的药物，也可使多种癌细胞发生凋亡。docetaxel（多烯紫杉醇）可使微管稳定。 水平基因转移胃癌细胞的转录组微阵列证明，lovostatin(洛伐他汀)能够显著抑制细胞分裂相关基因的表达，而docetaxel在转录方面作用甚微。两种药物都可以诱导凋亡，同时使用两种药物的效果大于单独使用两种药物效果的加和，即1+1>2。细胞周期抑制剂p21的表达显著上升，而激酶A和激酶B的表达减少，周期蛋白B1和D1在单独使用lovostatin，或联合使用docetaxel时表达都会减少。 两种药物治疗可使procaspase-3发生水解，抗凋亡Mcl-1蛋白、多聚ADP核糖聚合酶 和Bax的表达降低。 研究结果显示，联合使用lovostatin和docetaxel，或者单独使用lovostatin，都有理想的抗癌效果。（生物谷Bioon.com） The association of statins and taxanes: an efficient combination trigger of cancer cell apoptosis J Follet, L Corcos, G Baffet, F Ezan, F Morel, B Simon and C Le Jossic-Corcos Background: Cancer cell killing might be achieved by the combined use of available drugs. Statins are major anti-hypercholesterolemia drugs, which also trigger apoptosis of many cancer cell types, while docetaxel is a potent microtubule-stabilising agent. Methods: Here, we looked at the combined effects of lovastatin and docetaxel in cancer cells. Results: Whole transcriptome microarrays in HGT-1 gastric cancer cells demonstrated that lovastatin strongly suppressed expression of genes involved in cell division, while docetaxel had very little transcriptional effects. Both drugs triggered apoptosis, and their combination was more than additive. A marked rise in the cell-cycle inhibitor p21, together with reduction of aurora kinases A and B, cyclins B1 and D1 proteins was induced by lovastatin alone or in combination with docetaxel. The drug treatments induced the proteolytic cleavage of procaspase-3, a drop of the anti-apoptotic Mcl-1 protein, Poly-ADP-Ribose Polymerase and Bax. Strikingly, docetaxel-resistant HGT-1 cell derivatives overexpressing the MDR-1 gene were much more sensitive to lovastatin than docetaxel-sensitive cells. Conclusion: These results suggest that the association of lovastatin and docetaxel, or lovastatin alone, shows promise as plausible anticancer strategies, either as a direct therapeutic approach or following acquired P-glycoprotein-dependent resistance. |
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