Fingert H J, Kindy R L, Pardee A B
J Urol. 1984 Sep;132(3):609-13. doi: 10.1016/s0022-5347(17)49759-x.
Cytotoxicity of thiotepa or doxorubicin hydrochloride in human bladder cancer cells was investigated alone and in combination with methylxanthines. Methylxanthines can potentiate cytotoxicity of some DNA-damaging agents used in cancer therapy by preventing DNA repair. However, the potential clinical utility of these drug combinations has not been defined. Nontoxic concentrations of two methylxanthines, theobromine and caffeine, markedly enhanced lethality in T-24 human bladder cancer cells treated with thiotepa. Thiotepa cytotoxicity was increased over 10-fold by continuous treatment with nontoxic concentrations of methylxanthines (0.5 mM), but the major enhancing effect was observed in the 1st 24 hours after thiotepa exposure. By contrast, no such enhanced lethality was observed using higher methylxanthine concentrations and equal or greater cytotoxic treatments with doxorubicin hydrochloride. The amount of enhanced lethality by methylxanthines correlated directly with growth rate of the cells in culture, suggesting that differential enhanced therapeutic effects could be achieved in the treatment of superficial bladder tumors based on the increased proliferative rate of neoplastic bladder cells compared to normal bladder urothelium.
研究了噻替派或盐酸多柔比星对人膀胱癌细胞的细胞毒性，以及它们与甲基黄嘌呤联合使用时的细胞毒性。甲基黄嘌呤可通过阻止DNA修复来增强癌症治疗中使用的一些DNA损伤剂的细胞毒性。然而，这些药物组合的潜在临床效用尚未明确。两种甲基黄嘌呤（可可碱和咖啡因）的无毒浓度显著增强了噻替派处理的T-24人膀胱癌细胞的杀伤力。用无毒浓度的甲基黄嘌呤（0.5 mM）持续处理可使噻替派的细胞毒性增加10倍以上，但主要增强作用在噻替派暴露后的头24小时内观察到。相比之下，使用更高浓度的甲基黄嘌呤以及与盐酸多柔比星同等或更大细胞毒性的处理方法，未观察到这种增强的杀伤力。甲基黄嘌呤增强的杀伤力与培养细胞的生长速率直接相关，这表明与正常膀胱尿路上皮相比，基于肿瘤性膀胱细胞增殖速率的增加，在浅表膀胱肿瘤的治疗中可以实现不同的增强治疗效果。
