Hirose M, Takeda E, Ninomiya T, Kuroda Y, Miyao M
Department of Pediatrics, University of Tokushima, School of Medicine, Japan.
Br J Cancer. 1987 Oct;56(4):413-7. doi: 10.1038/bjc.1987.216.
The effects of combinations of dipyridamole, an effective blocker of the salvage pathway of DNA synthesis, and 8 types of anti-cancer drugs on the growth of human T, B and myeloid leukaemia/lymphoma cell lines in vitro were examined. In combinations, dipyridamole and vincristine (VCR), and dipyridamole and vindesine had synergistic inhibitory effects. Dipyridamole reduced the efflux of VCR from cells and enhanced their VCR accumulation in a dose-dependent manner at concentrations of up to 10 microM in the lymphoid cell lines, MOLT-3 and BL-TH, and of up to at least 20 microM in the myeloid cell line, ML-1. Dipyridamole also enhanced the accumulation of VCR in PHA-stimulated and un-stimulated lymphocytes of normal donors, but efflux of VCR was more rapid from normal lymphocytes than from cultured cell lines. It is proposed that combination therapy with dipyridamole plus VCR should be effective in the treatment of leukaemia and lymphoma.
研究了双嘧达莫(一种有效的DNA合成补救途径阻滞剂)与8种抗癌药物联合使用对人T、B和髓系白血病/淋巴瘤细胞系体外生长的影响。联合使用时,双嘧达莫与长春新碱(VCR)以及双嘧达莫与长春地辛具有协同抑制作用。在淋巴样细胞系MOLT-3和BL-TH中,浓度高达10 microM时,双嘧达莫以剂量依赖方式减少细胞内VCR的外流并增强其在细胞内的蓄积;在髓系细胞系ML-1中,浓度至少高达20 microM时也有此作用。双嘧达莫还增强了正常供体经PHA刺激和未经刺激的淋巴细胞内VCR的蓄积,但VCR从正常淋巴细胞中的外流比从培养细胞系中更快。有人提出,双嘧达莫加VCR的联合疗法在白血病和淋巴瘤治疗中应有效。