Nakaike S, Kashiwagi K, Terao K, Iio K, Igarashi K
Faculty of Pharmaceutical Sciences, Chiba University.
Jpn J Cancer Res. 1988 Apr;79(4):501-8. doi: 10.1111/j.1349-7006.1988.tb01619.x.
The antitumor and antimetastatic effects of alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, combined with an inhibitor of S-adenosylmethionine decarboxylase, either methylglyoxal bis(guanylhydrazone) (MGBG) or ethylglyoxal bis(guanylhydrazone) (EGBG), were studied in mice bearing P388 leukemia or Lewis lung carcinoma. Although EGBG is a more specific inhibitor of polyamine biosynthesis than the widely used MGBG, the antitumor effect of the DFMO-EGBG combination on P388 leukemia-bearing mice was less than that of the DFMO-MGBG combination. The prolongation of survival time by the DFMO(1000 mg/kg)-MGBG(25 mg/kg) combination was 2.65-fold, while that of the DFMO(1000 mg/kg)-EGBG(50 mg/kg) combination was 1.34-fold. When mice were fed a polyamine-deficient diet, stronger antitumor effects were exerted; the prolongation of survival time by the DFMO-MGBG and the DFMO-EGBG combinations was 2.89-fold and 2.03-fold, respectively. The antitumor effect of combined use of the two polyamine antimetabolites with mice on normal and polyamine-deficient diets correlated with a decrease of polyamine charge contents in the tumor cells. The above in vivo results were confirmed clearly in the KB cell culture system. The antimetastatic activity of DFMO on Lewis lung carcinoma-bearing mice was strengthened by the addition of MGBG or EGBG. The antimetastatic activity of the DFMO-MGBG or DFMO-EGBG combination did not parallel the polyamine charge contents in the primary tumor and blood.
鸟氨酸脱羧酶抑制剂α-二氟甲基鸟氨酸（DFMO）与S-腺苷甲硫氨酸脱羧酶抑制剂甲基乙二醛双（脒腙）（MGBG）或乙基乙二醛双（脒腙）（EGBG）联合使用对携带P388白血病或Lewis肺癌的小鼠的抗肿瘤和抗转移作用进行了研究。尽管EGBG是比广泛使用的MGBG更特异的多胺生物合成抑制剂，但DFMO-EGBG组合对携带P388白血病小鼠的抗肿瘤作用小于DFMO-MGBG组合。DFMO（1000 mg/kg）-MGBG（25 mg/kg）组合使生存时间延长2.65倍，而DFMO（1000 mg/kg）-EGBG（50 mg/kg）组合使生存时间延长1.34倍。当给小鼠喂食缺乏多胺的饮食时，会产生更强的抗肿瘤作用；DFMO-MGBG和DFMO-EGBG组合使生存时间延长分别为2.89倍和2.03倍。两种多胺抗代谢物联合使用对正常饮食和缺乏多胺饮食的小鼠的抗肿瘤作用与肿瘤细胞中多胺电荷含量的降低相关。上述体内结果在KB细胞培养系统中得到了明确证实。添加MGBG或EGBG可增强DFMO对携带Lewis肺癌小鼠的抗转移活性。DFMO-MGBG或DFMO-EGBG组合的抗转移活性与原发肿瘤和血液中的多胺电荷含量不平行。
