Villa R, Orlandi L, Berruti A, Dogliotti L, Zaffaroni N
Divisione di Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
Int J Oncol. 1999 Jan;14(1):133-8. doi: 10.3892/ijo.14.1.133.
The ability of mitotane, a DDT derivative with adrenotoxic activity, and lonidamine, an energolytic derivative of indazole-carboxylic acid, to modulate the cytotoxic activity of doxorubicin, epidoxorubicin, cisplatin and VP16 was investigated in a human adrenocortical carcinoma cell line (SW13). A marked variability in cellular response to a 1-h treatment with the individual anticancer agents was observed. The concentrations able to inhibit SW13 cell proliferation by 50% (IC50) were 0.45 microg/ml and 0.4 microg/ml for doxorubicin and epidoxorubicin, respectively, thus indicating a relative sensitivity to anthracyclines. Conversely, the SW13 cell line displayed a marked resistance to cisplatin (IC50, 13.9 microg/ml) and VP16 (IC50, 15 microg/ml). When cells were exposed to anticancer drugs and mitotane simultaneously or in sequence, a positive modulation of anthracycline cytotoxic effects was observed. Although to a lesser extent, mitotane also increased cisplatin activity. Conversely, no potentiation was observed when mitotane was combined with VP16. Lonidamine slightly increased the cytotoxicity of epirubicin and cisplatin as individual agents. Moreover, a supra-additive effect of the three-drug (epidoxorubicin-cisplatin-lonidamine) combination was observed.
研究了米托坦（一种具有肾上腺毒性活性的滴滴涕衍生物）和氯尼达明（一种吲唑羧酸的能量分解衍生物）对阿霉素、表阿霉素、顺铂和依托泊苷细胞毒性活性的调节能力，实验采用人肾上腺皮质癌细胞系（SW13）。观察到细胞对单独抗癌药物1小时处理的反应存在显著差异。阿霉素和表阿霉素抑制SW13细胞增殖50%（IC50）的浓度分别为0.45微克/毫升和0.4微克/毫升，表明对蒽环类药物相对敏感。相反，SW13细胞系对顺铂（IC50，13.9微克/毫升）和依托泊苷（IC50，15微克/毫升）表现出明显抗性。当细胞同时或依次暴露于抗癌药物和米托坦时，观察到蒽环类药物细胞毒性作用的正向调节。虽然程度较小，但米托坦也增强了顺铂的活性。相反，米托坦与依托泊苷联合使用时未观察到增效作用。氯尼达明作为单一药物时，略微增加了表柔比星和顺铂的细胞毒性。此外，观察到三种药物（表阿霉素-顺铂-氯尼达明）联合使用的超相加效应。
