2月14日,，BJC在線(xiàn)發(fā)表了法國(guó)研究人員的研究論文，他們發(fā)現(xiàn)聯(lián)合使用他汀類(lèi)藥物和紫杉醇可有效引發(fā)癌細(xì)胞凋亡,。
他汀類(lèi)是一種主要的治療高膽固醇血癥的藥物,，也可使多種癌細(xì)胞發(fā)生凋亡。docetaxel（多烯紫杉醇）可使微管穩(wěn)定,。
水平基因轉(zhuǎn)移胃癌細(xì)胞的轉(zhuǎn)錄組微陣列證明,，lovostatin(洛伐他汀)能夠顯著抑制細(xì)胞分裂相關(guān)基因的表達(dá)，而docetaxel在轉(zhuǎn)錄方面作用甚微,。兩種藥物都可以誘導(dǎo)凋亡,，同時(shí)使用兩種藥物的效果大于單獨(dú)使用兩種藥物效果的加和,，即1+1>2,。細(xì)胞周期抑制劑p21的表達(dá)顯著上升，而激酶A和激酶B的表達(dá)減少,，周期蛋白B1和D1在單獨(dú)使用lovostatin,，或聯(lián)合使用docetaxel時(shí)表達(dá)都會(huì)減少。
兩種藥物治療可使procaspase-3發(fā)生水解,，抗凋亡Mcl-1蛋白,、多聚ADP核糖聚合酶 和Bax的表達(dá)降低。
研究結(jié)果顯示,，聯(lián)合使用lovostatin和docetaxel,，或者單獨(dú)使用lovostatin，都有理想的抗癌效果,。（生物谷Bioon.com）
doi:10.1038/bjc.2012.6
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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.
