Van Belle S J, De Smet M C, De Mey J E, Storme G A
Oncology Center Vrije Universiteit Brussel, Cancer Research Unit, Belgium.
Anticancer Res. 1991 Jan-Feb;11(1):465-71.
Accumulation of vinblastine has been studied in different types of cancer cells. We measured the intracellular concentration of vinblastine in MO4 cells and compared it to its extracellular concentration in culture medium. We observed that the ratio of accumulation, expressed as the ratio of intracellular over extracellular vinblastine, was dose-dependent. An initial accumulation level was reached within 30 min and a second dose-induced level after 48 hours. This remained constant for another 5 days. Intracellular accumulation was also seen for vincristine and vindesine but here the phenomenon was less dose-dependent and the maximum level was reached after 6 hours. The accumulation ratio of a single vinca alkaloid in MO4 cells is not different from combined simultaneous exposure with 2 or 3 of the drugs. Energy blocking by sodium azide resulted in an inhibition of the supplementary but not the initial level of vinblastine accumulation. After washing out the medium for vinblastine the intracellular concentration remained about 60 micrograms/ml for 1 microgram/ml vinblastine added to the medium. Based on these results, it is concluded that the accumulation of vinblastine is only partially based on an energy mediated mechanism, in which binding of the drug to at least two types of sites may play an important role.
已对不同类型癌细胞中长春碱的蓄积情况进行了研究。我们测定了MO4细胞中长春碱的细胞内浓度，并将其与培养基中的细胞外浓度进行比较。我们观察到，蓄积比率（以细胞内长春碱与细胞外长春碱的比率表示）呈剂量依赖性。在30分钟内达到初始蓄积水平，48小时后出现第二次剂量诱导水平。此水平在接下来的5天内保持恒定。长春新碱和长春地辛也存在细胞内蓄积，但在此处该现象的剂量依赖性较小，且在6小时后达到最高水平。MO4细胞中单一长春花生物碱的蓄积比率与同时联合使用2种或3种药物时并无差异。叠氮化钠导致的能量阻断抑制了长春碱蓄积的补充水平，但未抑制初始水平。在洗去培养基中的长春碱后，对于添加到培养基中1微克/毫升的长春碱，细胞内浓度保持在约60微克/毫升。基于这些结果，得出结论：长春碱的蓄积仅部分基于能量介导机制，其中药物与至少两种类型位点的结合可能起重要作用。
