Silvestrini R, Zaffaroni N, Villa R, Orlandi L, Costa A
Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Int J Cancer. 1992 Nov 11;52(5):813-7. doi: 10.1002/ijc.2910520524.
The ability of lonidamine, an energolytic derivative of indazole-carboxylic acid, to modulate the cytotoxicity of cisplatin was investigated in human ovarian-cancer cell lines sensitive (A2780) or with experimentally induced resistance (A2780/cp8) to the alkylating agent. A 24-hr post-incubation with 300 microM lonidamine significantly potentiated the activity of a 1-hr cisplatin treatment in both cell lines. In particular, the cisplatin IC50 value was reduced 4-fold in the sensitive line and 5-fold in the resistant line. Flow cytometric analysis showed that, in the resistant cell line, lonidamine alone did not affect cell kinetics, but when given after cisplatin it was able to transform the temporary G2 + M cell accumulation induced by the alkylating agent to a persistent block in S/G2 + M. In the A2780/cp8 cell line, lonidamine was also able to significantly enhance the accumulation of cisplatin-induced DNA interstrand cross-links. Our results suggest that lonidamine can positively modulate the anti-tumor activity of cisplatin in ovarian cancer cells and also indicate that the drug is potentially useful in combination therapy including the alkylating agent for ovarian cancer patients.
研究了吲唑羧酸的能量分解衍生物氯尼达明对顺铂细胞毒性的调节作用，实验对象为对烷化剂敏感（A2780）或经实验诱导产生抗性（A2780/cp8）的人卵巢癌细胞系。在两种细胞系中，与300微摩尔氯尼达明共同孵育24小时后，显著增强了1小时顺铂处理的活性。特别是，顺铂在敏感细胞系中的IC50值降低了4倍，在耐药细胞系中降低了5倍。流式细胞术分析表明，在耐药细胞系中，单独使用氯尼达明不影响细胞动力学，但在顺铂给药后使用时，它能够将烷化剂诱导的暂时G2+M期细胞积累转变为S/G2+M期的持续阻滞。在A2780/cp8细胞系中，氯尼达明还能够显著增强顺铂诱导的DNA链间交联的积累。我们的结果表明，氯尼达明可以正向调节顺铂在卵巢癌细胞中的抗肿瘤活性，并且还表明该药物在包括烷化剂在内的卵巢癌患者联合治疗中具有潜在用途。
