Comparison of the effects of vinblastine, vincristine, vindesine, and vinepidine on microtubule dynamics and cell proliferation in vitro.
Comparison of the effects of vinblastine, vincristine, vindesine, and vinepidine on microtubule dynamics and cell proliferation in vitro.
复制标题
DOI：
--
复制
发表时间：
1985-06
期刊：
影响因子：
11.2
通讯作者：
M. Jordan;R. Himes;L. Wilson
中科院分区：
文献类型：
--
作者：
M. Jordan;R. Himes;L. Wilson
长春新碱的新衍生物Vinepidine和临床上使用的三种长春花衍生物长春碱、长春新碱和长春地辛被检查了它们在稳态下抑制牛脑微管组装末端的净微管蛋白添加的能力。虽然所有四种衍生物在效力上大体相似，但它们抑制微管蛋白添加的相对能力是可区分的。Vinepidine和长春新碱是最有效的衍生物（Ki，分别为0.079 +/- 0.018（SD）microM和0.085 +/- 0.013 microM），其次是长春地辛（Ki，0.110 +/- 0.007 microM）和长春碱（Ki，0.178 +/- 0.025 microM）。与其在体外抑制微管组装的相对能力相反，长春碱及其衍生物长春地辛在抑制培养中的细胞增殖方面通常比长春新碱和长春哌啶更有效。在B16黑色素瘤细胞中，长春碱的效力是最弱的衍生物vinepidine的9倍。在L-细胞中，长春碱在40 nM时完全抑制生长，而长春新碱和长春地辛引起约25%的抑制，并且vinepidine无活性。当B16黑色素瘤细胞在注射到小鼠体内之前用药物处理时，长春地辛（四种体外衍生物中较弱的一种）最能抑制肿瘤生长。结果表明，长春花衍生物之间的化学差异，这在很小程度上影响的衍生物的能力，抑制微管组装在体外，导致显着差异的顺序和大小的药物抑制细胞生长的能力。
Vinepidine, a new derivative of vincristine, and three clinically used Catharanthus derivatives, vinblastine, vincristine, and vindesine, were examined for their abilities to inhibit net tubulin addition at the assembly ends of bovine brain microtubules at steady state. Although all four derivatives were generally similar in potency, their relative abilities to inhibit tubulin addition were distinguishable. Vinepidine and vincristine were the most potent derivatives (Ki, 0.079 +/- 0.018 (SD) microM and 0.085 +/- 0.013 microM, respectively), followed by vindesine (Ki, 0.110 +/- 0.007 microM) and vinblastine (Ki, 0.178 +/- 0.025 microM). In contrast to their relative abilities to inhibit microtubule assembly in vitro, vinblastine and its derivative, vindesine, were generally more potent than vincristine and vinepidine in inhibiting cell proliferation in culture. Vinblastine was nine times more potent than the weakest derivative, vinepidine, in B16 melanoma cells. In L-cells, vinblastine completely inhibited growth at 40 nM, whereas vincristine and vindesine caused about 25% inhibition, and vinepidine was inactive. When B16 melanoma cells were treated with drug before being injected into mice, retardation of tumor growth was best achieved with vindesine, one of the weaker of the four derivatives in vitro. The results demonstrate that chemical differences among the Catharanthus derivatives, which affect to small extents the abilities of the derivatives to inhibit microtubule assembly in vitro, result in significant differences in the order and the magnitude of the abilities of the drugs to inhibit cell growth.