Fujimoto S, Shrestha R D, Ohta M, Igarashi K, Kokubun M, Okui K, Fujita M, Taguchi T
1st Dept. of Surgery, School of Medicine, Chiba University.
Gan To Kagaku Ryoho. 1987 Oct;14(10):2930-5.
Treatment of nude mice xenografted with human gastric cancer was carried out by polyamine antimetabolites combined with mitomycin C (MMC) and polyamine-free diet. Polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) and ethylglyoxal-bis-guanylhydrazone (EGBG), were given ip in a daily dose of 1,000 mg/kg and 20 mg/kg, respectively, for 6 consecutive days. MMC 2.0 mg/kg was administered every other day. The polyamine-free diet was given from 4 days before start of the treatment through the end of the study. Although the tumor growth rate of the control group given polyamine-free diet was similar to that given normal diet, in the mice treated with EGBG, DFMO plus MMC, the antitumor effect in the polyamine-free diet group was superior to the normal diet group. In comparison with tumor growth suppression due to EGBG plus DFMO or MMC only, the polyamine-free diet group showed better result than the normal diet group to some extent. In mice treated with EGBG, DFMO plus MMC, tumor tissue spermine levels in the polyamine-free diet group were significantly depressed, compared to the normal diet group. Furthermore, marked suppression of DNA biosynthesis was observed in mice given EGBG, DFMO plus MMC together with the polyamine-free diet. These results suggest that combined treatments of polyamine antimetabolites and MMC revealed a marked enhancement of antitumor effects, under conditions of polyamine depletion, which may be responsible for the alteration in DNA structure.
采用多胺抗代谢物联合丝裂霉素C（MMC）及无多胺饮食对人胃癌裸鼠移植瘤进行治疗。多胺抗代谢物，即α-二氟甲基鸟氨酸（DFMO）和乙二醛双脒腙（EGBG），分别以每日1000mg/kg和20mg/kg的剂量腹腔注射，连续6天。每间隔一天给予2.0mg/kg的MMC。从治疗开始前4天至研究结束给予无多胺饮食。尽管给予无多胺饮食的对照组肿瘤生长速率与给予正常饮食的对照组相似，但在用EGBG、DFMO加MMC治疗的小鼠中，无多胺饮食组的抗肿瘤效果优于正常饮食组。与仅由EGBG加DFMO或MMC引起的肿瘤生长抑制相比，无多胺饮食组在一定程度上比正常饮食组效果更好。在用EGBG、DFMO加MMC治疗的小鼠中，与正常饮食组相比，无多胺饮食组肿瘤组织中的精胺水平显著降低。此外，在给予EGBG、DFMO加MMC并同时给予无多胺饮食的小鼠中观察到DNA生物合成受到明显抑制。这些结果表明，在多胺耗竭的条件下，多胺抗代谢物与MMC联合治疗显示出显著增强的抗肿瘤作用，这可能与DNA结构的改变有关。
