A study on overcoming the drug resistance to sarcoma

在这项研究中，抗癌药物和咖啡因，抑制DNA修复，对人类肉瘤的联合作用进行了研究与各种检测技术。在人肿瘤克隆形成实验中，咖啡因与顺铂、丝裂霉素C、环磷酰胺和阿霉素四种DNA损伤剂联合使用产生协同作用。特别是通过顺铂与咖啡因的组合，在18个新鲜人肿瘤标本中的14个（78%）中观察到显著的协同效应。有丝分裂后，咖啡因显著增加顺铂的杀细胞作用。此时，在DNA直方图上S和G2/M期的积累减少，并且经常观察到肿瘤细胞的核碎片。在实验中，采用无胸腺小鼠，咖啡因和顺铂的组合显示出显着的抗肿瘤作用，而没有显着的毒性。这些发现表明，咖啡因可能是一种有用的药物，能够克服肉瘤的耐药性，因为咖啡因增强了DNA损伤剂的作用。

In this study the combined effect of anticancer agents and caffeine, which inhibits DNA repair, on human sarcomas was examined with various assay techniques. In human tumor clonogenic assay, the combined use of caffeine produced synergistic effects with four DNA-damaging agents (cisplatin, mitomycin C, cyclophosphamide and adriamycin). Particularly by the combination of cisplatin with caffeine, marked synergistic effects were observed in 14 out of 18 specimens (78%) of fresh human tumor specimens. Caffeine markedly increased the cytocidal effect of cisplatin following mitosis. At this time, the accumulation of S and G2/M phase was reduced on the DNA histogram, and nuclear fragmentations of tumor cells were frequently observed. In assay, using athymic mice, the combination of caffeine and cisplatin showed prominent antitumor effect without significant toxicity. These findings suggest the possibility that caffeine could be a useful drug capable of overcoming drug resistance to sarcomas, as caffeine enhanced the effect of DNA-damaging agents.