Stein C A
Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Semin Oncol. 1999 Oct;26(5 Suppl 17):3-7.
Taxanes appear to have significant clinical activity in hormone-refractory prostate cancer and are entering increasing numbers of clinical trials. In general, they appear to initiate the apoptotic process by binding to beta-tubulin and promoting its polymerization. However, it is possible, at least in prostate cancer cell lines, that the ultimate decision for or against apoptosis may be modulated by a number of factors, including levels of Bcl-family members, especially the antiapoptotic proteins bcl-2 and bcl-xL. Differences in the cellular pharmacology of docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) and paclitaxel have been identified. Docetaxel has a somewhat higher affinity for microtubules than paclitaxel (approximately twofold), and in some circumstances may be a more potent inducer of bcl-2 phosphorylation. However, it is not clear whether these docetaxel-induced events are directly related to its antiprostate cancer effects. In murine macrophages, paclitaxel, but not docetaxel, induces several proinflammatory genes, but it is not known whether this occurs in prostate cancer cells. The mechanisms of cytotoxicity of taxanes in prostate cancer are undoubtedly complex and will require considerable additional study to fully understand.
紫杉烷类药物在激素难治性前列腺癌中似乎具有显著的临床活性，并且正在进入越来越多的临床试验。一般来说，它们似乎通过与β-微管蛋白结合并促进其聚合来启动凋亡过程。然而，至少在前列腺癌细胞系中，支持或反对凋亡的最终决定可能受到多种因素的调节，包括Bcl-家族成员的水平，尤其是抗凋亡蛋白bcl-2和bcl-xL。已发现多西他赛（泰索帝；罗纳普朗克·罗雷尔公司，宾夕法尼亚州学院村）和紫杉醇在细胞药理学方面存在差异。多西他赛对微管的亲和力比紫杉醇略高（约两倍），在某些情况下可能是bcl-2磷酸化的更有效诱导剂。然而，尚不清楚这些多西他赛诱导的事件是否与其抗前列腺癌作用直接相关。在鼠巨噬细胞中，紫杉醇而非多西他赛可诱导几种促炎基因，但尚不清楚这是否发生在前列腺癌细胞中。紫杉烷类药物在前列腺癌中的细胞毒性机制无疑是复杂的，需要进行大量额外研究才能完全理解。
