Yamagami K, Fujii A, Arita M, Okumoto T, Sakata S, Matsuda A, Ueda T, Sasaki T
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Saitama, Japan.
Cancer Res. 1991 May 1;51(9):2319-23.
The antitumor activity of 2'-deoxy-2'-methylidenecytidine (DMDC), an inhibitor of DNA synthesis, was examined and compared with that of 1-beta-D-arabinofuranosylcytosine (ara-C) against various murine tumors and human tumor xenografts. Against P388 murine leukemia, repeated treatments of DMDC were more effective than its single administration. Interestingly, DMDC was effective against colon 26 murine carcinoma, M5076 murine reticulum cell sarcoma, LX-1 human lung cancer xenograft, and SK-Mel-28 human melanoma xenograft, which are less sensitive or refractory to ara-C, while DMDC was not more potent against murine leukemias P388 and L1210 than ara-C. The in vitro cytotoxic effects of DMDC and ara-C against L1210 leukemia cells were prevented dose dependently by deoxycytidine, suggesting that DMDC, like ara-C, may require phosphorylation by deoxycytidine kinase for antitumor activity. DMDC was effective against human and murine experimental tumor models, especially nonleukemic tumors refractory to ara-C, suggesting that DMDC will be a promising agent for the treatment of cancer.
对DNA合成抑制剂2'-脱氧-2'-亚甲基胞苷（DMDC）的抗肿瘤活性进行了检测，并将其与1-β-D-阿拉伯呋喃糖基胞嘧啶（阿糖胞苷）针对多种小鼠肿瘤和人肿瘤异种移植的活性进行了比较。对于P388小鼠白血病，重复给予DMDC比单次给药更有效。有趣的是，DMDC对结肠26小鼠癌、M5076小鼠网状细胞肉瘤、LX-1人肺癌异种移植瘤和SK-Mel-28人黑色素瘤异种移植瘤有效，这些肿瘤对阿糖胞苷不太敏感或耐药，而DMDC对小鼠白血病P388和L1210的效力并不比阿糖胞苷更强。脱氧胞苷可剂量依赖性地抑制DMDC和阿糖胞苷对L1210白血病细胞的体外细胞毒性作用，这表明DMDC与阿糖胞苷一样，可能需要脱氧胞苷激酶磷酸化才能发挥抗肿瘤活性。DMDC对人和小鼠实验性肿瘤模型有效，尤其是对阿糖胞苷耐药的非白血病肿瘤，这表明DMDC将是一种有前景的癌症治疗药物。
