Non-antitumor vinca alkaloids reverse multidrug resistance in P388 leukemia cells in vitro.
Non-antitumor vinca alkaloids reverse multidrug resistance in P388 leukemia cells in vitro.
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非抗肿瘤长春花生物碱可在体外逆转 P388 白血病细胞的多药耐药性。
DOI：
10.20772/cancersci1985.77.2_197
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
K. Nagashima
中科院分区：
文献类型：
--
作者：
M. Inaba;K. Nagashima
玫瑰花中的12种单体或二聚体生物碱，已报道具有很少或没有抗肿瘤活性，以确定它们与长春新碱或柔红霉素对耐长春新碱和对蒽环类交叉耐药的P388亚系体外细胞生长的联合作用。我们发现，在亚细胞毒性浓度的组合诱导显着的耐药细胞的生长抑制，但不敏感的细胞。在所检测的生物碱中，长春碱、文多灵、长春质碱、长春定和洛赫讷碱能够完全抑制细胞生长。使用文多灵的进一步体外研究显示，在10微克/毫升时，它不仅能够完全逆转对长春新碱的耐药性，而且能够完全逆转对长春碱、柔红霉素和阿霉素的交叉耐药性。此外，我们还发现，具有逆转耐药性活性的长春花生物碱具有增强耐药细胞对长春新碱和柔红霉素的净摄取的有效活性，并且这种作用被证明是由于它们对主动外排过程的抑制作用。这些结果为我们的假设提供了进一步的支持，即蒽环类药物和长春花生物碱都可以通过与细胞膜相互作用来抑制它们自己的外排过程，并且这种相似性为它们的相互交叉抗性提供了基础，而不管它们的不同化学结构。
Twelve monomeric or dimeric alkaloids from Vinca rosea Linn., which had been reported to have little or no antitumor activity, were investigated to determine their combined effects with either vincristine or daunorubicin on in vitro cell growth of a P388 subline resistant to vincristine and cross-resistant to anthracyclines. We found that the combinations at subcytotoxic concentrations induced significant growth inhibition of the resistant cells, but not of the sensitive cells. Of the alkaloids examined, catharine, vindoline, catharanthine, vincarodine, and lochnerine were able to bring about complete inhibition of cell growth. Further in vitro study using vindoline revealed that at 10 micrograms/ml it was able to completely reverse not only resistance to vincristine but also cross-resistance to vinblastine, daunorubicin, and adriamycin. In addition, we found that vinca alkaloids active in reversing resistance possess potent activities to enhance the net uptake of not only vincristine but also daunorubicin by the resistant cells, and this effect was proved to result from their inhibitory action on the active efflux process. These results provide further support for our hypothesis that both anthracyclines and vinca alkaloids can inhibit their own efflux process by interacting with the cell membrane, and this similarity provides a basis for their reciprocal cross-resistance, irrespective of their different chemical structures.
P388 小鼠白血病的蒽环类药物耐药性及其钙拮抗剂的规避。
影响因子：
11.2
作者：
Kessel,D;Wilberding,C
通讯作者：
Wilberding,C
改变蒽环类药物耐药性的钙拮抗剂的作用方式。
影响因子：
5.8
作者：
Kessel,D;Wilberding,C
通讯作者：
Wilberding,C