Miyoshi T, Ogawa S, Nobuhara M, Namba M
Gan To Kagaku Ryoho. 1984 Mar;11(3):440-4.
Inosiplex, a 3:1 molarcomplex of N, N-dimethylamino-2-propanol-p-acetamidobenzoate and inosine, which has been reported to exhibit antiviral activity in vitro and in vivo, enhanced cytotoxic effects of 5-fluorouracil (5-FU). Effects of inosiplex on the potentiation of cytotoxicity of 5-FU were investigated in vitro and in vivo. In vitro studies demonstrated that cytotoxic effects of 5-FU on cloning efficiency of HeLa cells were prominently enhanced by inosiplex, while inosiplex alone showed no cytotoxicity at the concentrations examined. Further, the survival time of mice intraperitoneally inoculated with Ehrlich ascites tumor cells was investigated. The mean survival time of mice treated with the combination of 5-FU and inosiplex significantly prolonged as compared with that of control animals or mice treated with inosiplex alone or 5-FU alone. Since inosiplex has been clinically studied as an antiviral agent and proved to be harmless to humans, the present results indicate that a combined administration of 5-FU and inosiplex may be effective in the treatment of human cancers.
肌苷多聚次黄嘌呤核苷酸(Inosiplex)是N,N - 二甲基氨基 - 2 - 丙醇 - 对乙酰氨基苯甲酸盐与肌苷的3:1摩尔复合物,据报道其在体外和体内均表现出抗病毒活性,它增强了5 - 氟尿嘧啶(5 - FU)的细胞毒性作用。对肌苷多聚次黄嘌呤核苷酸增强5 - FU细胞毒性的作用进行了体外和体内研究。体外研究表明,肌苷多聚次黄嘌呤核苷酸显著增强了5 - FU对HeLa细胞克隆效率的细胞毒性作用,而在检测的浓度下,肌苷多聚次黄嘌呤核苷酸单独使用时未显示出细胞毒性。此外,还研究了腹腔接种艾氏腹水瘤细胞的小鼠的存活时间。与对照动物或单独用肌苷多聚次黄嘌呤核苷酸或5 - FU处理的小鼠相比,用5 - FU和肌苷多聚次黄嘌呤核苷酸联合处理的小鼠的平均存活时间显著延长。由于肌苷多聚次黄嘌呤核苷酸已作为抗病毒药物进行了临床研究并被证明对人体无害,目前的结果表明5 - FU和肌苷多聚次黄嘌呤核苷酸联合给药可能对人类癌症的治疗有效。