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多西他赛/唑来膦酸联合用药通过下调激素难治性前列腺癌细胞中抗凋亡Bcl-2蛋白水平协同触发细胞凋亡。

Docetaxel/zoledronic acid combination triggers apoptosis synergistically through downregulating antiapoptotic Bcl-2 protein level in hormone-refractory prostate cancer cells.

作者信息

Karabulut B, Erten C, Gul M K, Cengiz E, Karaca B, Kucukzeybek Y, Gorumlu G, Atmaca H, Uzunoglu S, Sanli U A, Baran Y, Uslu R

机构信息

Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, Bornova, Izmir, Turkey.

出版信息

Cell Biol Int. 2009 Feb;33(2):239-46. doi: 10.1016/j.cellbi.2008.11.011. Epub 2008 Dec 11.

Abstract

Docetaxel, a semi-synthetic taxane analogue, is used effectively in the treatment of metastatic prostate cancer. Zoledronic acid, the most potent member of bisphosphonates, has shown pleiotropic anti-tumoral effects on prostate cancer cells. We have explored the possible additive/synergistic effects and the apoptotic pathways induced by combination treatment of docetaxel and zoledronic acid in hormone and drug refractory, PC-3 and DU-145 prostate cancer cells. Combination of docetaxel and zoledronic acid synergistically inhibits cell growth in PC-3 and DU-145 cells. Moreover, this effect was due to downregulation of antiapoptotic protein Bcl-2 in PC-3 and DU-145 cells. In conclusion, docetaxel/zoledronic acid combination is potentially a novel and effective approach for the treatment of prostate cancer.

摘要

多西他赛是一种半合成紫杉烷类似物,在转移性前列腺癌的治疗中疗效显著。唑来膦酸是双膦酸盐类中活性最强的一种,已显示出对前列腺癌细胞具有多效性抗肿瘤作用。我们探究了多西他赛与唑来膦酸联合治疗对激素难治型和药物难治型PC-3及DU-145前列腺癌细胞可能产生的相加/协同效应以及诱导的凋亡途径。多西他赛与唑来膦酸联合用药可协同抑制PC-3和DU-145细胞的生长。此外,这种效应是由于PC-3和DU-145细胞中抗凋亡蛋白Bcl-2的下调所致。总之,多西他赛/唑来膦酸联合用药可能是一种治疗前列腺癌的新型有效方法。

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