Akiyama S I, Hidaka K, Komiyama S, Kuwano M
Cancer Res. 1979 Dec;39(12):5150-4.
Control of permeation of bleomycin A2, a well-known antitumor antibiotic, in combination with various polyene macrolide antibiotics was analyzed in cultured Chinese hamster cells in vitro. Three polyene antibiotics, filipin, pentamycin, and pimaricin, were found to enhance the action of bleomycin A2 remarkably, while amphotericin B or nystatin could not. Although DNA synthesis and colony-forming activity of polyene-sensitive Chinese hamster V79 cells were synergistically inhibited by the combination of filipin and bleomycin A2, in a polyene-resistant subline (AMBR-1) derived from V79, they were only slightly affected in the presence of both drugs. The cellular uptake of [14C]bleomycin A2 by V79 was enhanced 2- to 4-fold in the presence of increasing doses of filipin or pentamycin, but not in the presence of amphotericin B. The treatment of V79 cells with filipin for 20 to 30 min was enought to block DNA synthesis almost completely when combined with 20 microgram belomycin A2 per ml. The pretreatment of the hamster cells with 6 microgram filipin per ml for 60 min continued to enhance the inhibitory action by bleomycin A2 of DNA synthesis up to 5 hr after the removal of filipin from the cultured medium.
在体外培养的中国仓鼠细胞中，分析了著名的抗肿瘤抗生素博来霉素A2与各种多烯大环内酯类抗生素联合使用时的渗透控制情况。发现三种多烯抗生素，即制霉菌素、戊霉素和匹马霉素，能显著增强博来霉素A2的作用，而两性霉素B或制霉菌素则不能。虽然制霉菌素和博来霉素A2联合使用可协同抑制多烯敏感的中国仓鼠V79细胞的DNA合成和集落形成活性，但在源自V79的多烯抗性亚系（AMBR-1）中，两种药物同时存在时它们仅受到轻微影响。在存在递增剂量的制霉菌素或戊霉素时，V79细胞对[14C]博来霉素A2的细胞摄取增强了2至4倍，但在存在两性霉素B时则没有增强。当每毫升培养基中加入20微克博来霉素A2时，用制霉菌素处理V79细胞20至30分钟足以几乎完全阻断DNA合成。用每毫升6微克制霉菌素预处理仓鼠细胞60分钟后，在从培养基中去除制霉菌素后的长达5小时内，博来霉素A2对DNA合成的抑制作用持续增强。
