Pradhan S G, Chitnis M P, Basrur V S, Tantri S K
Eur J Cancer Clin Oncol. 1987 Apr;23(4):437-42. doi: 10.1016/0277-5379(87)90383-x.
Experiments were carried out in vitro on adriamycin (ADR) accumulation and cytotoxicity alone and in combination with calcium channel antagonist, verapamil (VRP), in ascites murine tumour models of Ehrlich carcinoma (EAC), sarcoma 180 (S180) and P388 lymphocytic leukaemia (P388). The cytotoxicity was assayed as the inhibition of [3H]-thymidine incorporation into the cellular DNA. ADR, a broad-spectrum anticancer drug, at a concentration of 10 micrograms/ml showed a cytotoxic effect in the order S180 greater than P388 greater than EAC. VRP alone exhibited the DNA synthesis inhibiting activity. The enhanced DNA biosynthesis inhibition of ADR along with VRP was maximal in S180 and marginal in P388 and EAC. The ADR retention after 3 hr of incubation in these tumour models correlated with the cytotoxicity. VRP enhanced the accumulation of ADR in all these cell lines. The property of potentiation in the activity and accumulation of ADR in these tumours exposed to a non-toxic concentration of VRP can best be utilized in cancer chemotherapy where the massive cytotoxic therapy, with a single large dose of ADR, can be substituted with a low dose, along with this drug-response modulator, for better therapeutic results.
在体外对阿霉素（ADR）单独以及与钙通道拮抗剂维拉帕米（VRP）联合使用时在艾氏腹水癌（EAC）、肉瘤180（S180）和P388淋巴细胞白血病（P388）的腹水小鼠肿瘤模型中的蓄积和细胞毒性进行了实验。细胞毒性通过检测[3H] - 胸腺嘧啶掺入细胞DNA的抑制率来测定。ADR是一种广谱抗癌药物，浓度为10微克/毫升时，其对S180、P388和EAC的细胞毒性作用依次为S180＞P388＞EAC。单独的VRP表现出DNA合成抑制活性。ADR与VRP联合使用时对DNA生物合成的抑制增强，在S180中最大，在P388和EAC中则较轻微。在这些肿瘤模型中孵育3小时后ADR的滞留情况与细胞毒性相关。VRP增强了ADR在所有这些细胞系中的蓄积。在暴露于无毒浓度VRP的这些肿瘤中，ADR的活性和蓄积增强的特性在癌症化疗中最能得到利用，在癌症化疗中，用单一高剂量ADR进行的大规模细胞毒性治疗可以用低剂量ADR与这种药物反应调节剂联合使用来替代，以获得更好的治疗效果。
