Rao P N, Wang Y C, Lotzova E, Khan A A, Rao S P, Stephens L C
Cancer Chemother Pharmacol. 1985;15(1):20-5. doi: 10.1007/BF00257288.
Since the male antifertility drug, gossypol, was shown to be a specific inhibitor of DNA synthesis at moderately low doses in cultured cells, its antitumor potential has been evaluated in three murine tumor models. The effects of gossypol on tumor growth and the survival of 10- to 12-week-old BDF1 mice bearing mouse mammary adenocarcinoma 755 (Ca 755) or P388 or L1210 leukemias, all injected IP, were measured. At an optimum dose of 0.5 mg/mouse given as a single injection at 2 days (48 h) after the inoculation of 10(5) Ca 755 tumor cells, gossypol rendered 66% of the mice free of tumor cells, whereas the remaining 34% died of drug toxicity. The survival rate decreased sharply at doses on either side of the optimum. At suboptimal doses a major proportion of the tumor-bearing mice died of tumor, whereas at higher doses all the animals died of drug toxicity. In other words, the effective dose range of gossypol was rather narrow. The rapidly proliferating mouse leukemias, P388 and L1210, failed to respond to gossypol. Histopathological studies of various organs in the gossypol-treated mice revealed no consistent lesions that could give an indication of organ-specific toxicity of gossypol. The reduction in the myeloid series in the bone marrow of gossypol-treated mice may have been due to depletion rather than direct toxic effect. Further studies are essential to evaluate this compound with regard to its antitumor activity in other murine models.
由于男性抗生育药物棉酚在培养细胞中以中等低剂量显示出是DNA合成的特异性抑制剂，因此已在三种小鼠肿瘤模型中评估了其抗肿瘤潜力。测量了棉酚对10至12周龄BDF1小鼠的肿瘤生长和存活的影响，这些小鼠接种了小鼠乳腺腺癌755（Ca 755）或P388或L1210白血病，均通过腹腔注射。在接种10(5)个Ca 755肿瘤细胞后2天（48小时）以0.5毫克/小鼠的最佳剂量单次注射，棉酚使66%的小鼠无肿瘤细胞，而其余34%死于药物毒性。在最佳剂量两侧的剂量下，存活率急剧下降。在次优剂量下，大部分荷瘤小鼠死于肿瘤，而在更高剂量下，所有动物均死于药物毒性。换句话说，棉酚的有效剂量范围相当窄。快速增殖的小鼠白血病P388和L1210对棉酚没有反应。对棉酚处理的小鼠的各种器官进行的组织病理学研究显示，没有一致的病变可以表明棉酚的器官特异性毒性。棉酚处理的小鼠骨髓中髓系细胞的减少可能是由于耗竭而不是直接毒性作用。关于该化合物在其他小鼠模型中的抗肿瘤活性，还需要进一步研究来评估。
