Haveman J, Bergs J W J, Franken N A P, van Bree C, Stalpers L J A
Academic Medical Centre, Department of Radiotherapy, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
Oncol Rep. 2005 Aug;14(2):561-7. doi: 10.3892/or.14.2.561.
The cytotoxicity of cisplatin, applied alone or in combination with hyperthermia, to mouse mammary adenocarcinoma cells (M8013S) was studied with the cells either treated in medium [Eagle's minimum essential medium (MEM), supplemented with 10% foetal bovine serum, 100 IU/ml penicillin, 200 mM glutamine and 0.35 g/l NaHCO(3)] or in Hank's balanced salt solution (HBSS) without serum. To study the role of platinum uptake by the M8013 cells in cytotoxicity, uptake was determined under conditions similar to those used in the survival experiments. Our results show that hyperthermia (30 min at 43 degrees C) enhances the toxicity of cisplatin. Enhanced toxicity by heat treatment is not observed with the cells in HBSS. The thermal enhancement of effects of cisplatin to cells in MEM with serum is clearly related to an enhanced uptake of cisplatin. A novel observation is that in order to obtain a considerable thermal enhancement of the cytotoxic effect of cisplatin, the exposure of the cells to the drug is required not only during the hyperthermic treatment but the exposure has to be maintained for at least 2 h after hyperthermia. These same conditions are also required for enhanced uptake of cisplatin. The present results may indicate that cisplatin has to be bound to some serum component in order to facilitate an 'active' uptake. Hyperthermia leads to a considerable intracellular accumulation of cisplatin, relative to the extracellular concentration. This accumulation takes place during exposure to cisplatin but after heat treatment.
研究了单独使用顺铂或联合热疗对小鼠乳腺腺癌细胞（M8013S）的细胞毒性，细胞分别在培养基[伊格尔氏最低必需培养基（MEM），补充有10%胎牛血清、100 IU/ml青霉素、200 mM谷氨酰胺和0.35 g/l碳酸氢钠（NaHCO₃）]或无血清的汉克平衡盐溶液（HBSS）中处理。为了研究M8013细胞摄取铂在细胞毒性中的作用，在与生存实验相似的条件下测定摄取情况。我们的结果表明，热疗（43℃30分钟）增强了顺铂的毒性。在HBSS中的细胞未观察到热处理增强的毒性。顺铂对含血清的MEM中的细胞的热增强效应显然与顺铂摄取增加有关。一个新的观察结果是，为了获得顺铂细胞毒性效应的显著热增强，不仅在热疗期间需要使细胞暴露于药物，而且在热疗后暴露必须持续至少2小时。顺铂摄取增加也需要相同的条件。目前的结果可能表明，顺铂必须与某些血清成分结合以促进“主动”摄取。相对于细胞外浓度，热疗导致顺铂在细胞内大量积累。这种积累发生在暴露于顺铂期间，但在热处理之后。
