[多胺抗代谢物与顺二氨二氯铂的联合疗效]

[Combined efficacy of polyamine antimetabolites and cis-diamminedichloroplatinum].

作者信息

Fujimoto S, Shrestha R D, Ohta M, Kokubun M, Igarashi K, Endoh F, Miyazaki M, Shimura T, Takahashi O, Kawata S

出版信息

Gan No Rinsho. 1986 Dec;32(15):1929-33.

Abstract

The combined antitumor effects of the polyamine antimetabolites, alpha-difluoro methylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), with CDDP were studied using human gastric cancer cells xenotransplanted into nude mice. DFMO (1000 mg/kg in two divided doses) and MGBG (50 mg/kg) were given IP for six consecutive days from the time when the xenotransplanted tumor weighted about 100 mg, and CDDP (3.0 mg/kg) was given IP every other day from the same time. Animals treated with DFMO plus MGBG with or without CDDP as well as with CDDP only displayed suppressed tumor growth, compared to untreated mice. In mice treated with these three drugs, however, tumor growth was rather rapid compared to those treated with CDDP only, although tumoral CDDP levels in animals given DFMO, MGBG and CDDP were higher than those given CDDP only. When DFMO, MGBG and CDDP or DFMO and MGBG were administered, tumoral spermidine and spermine levels decreased markedly. On the other hand, tumor DNA biosynthesis in the CDDP only group dropped markedly 24 hours after the termination of therapy. These results suggest that an alteration in the DNA structure caused by polyamine deficiency may prevent cross-link formation in DNA by CDDP.

摘要

使用移植到裸鼠体内的人胃癌细胞，研究了多胺抗代谢物α-二氟甲基鸟氨酸（DFMO）和甲基乙二醛双脒腙（MGBG）与顺铂（CDDP）联合的抗肿瘤作用。从异种移植肿瘤重量约为100mg时起，连续6天腹腔注射DFMO（1000mg/kg，分两次给药）和MGBG（50mg/kg），并从同一时间开始每隔一天腹腔注射CDDP（3.0mg/kg）。与未治疗的小鼠相比，接受DFMO加MGBG联合或不联合CDDP以及仅接受CDDP治疗的动物肿瘤生长受到抑制。然而，在接受这三种药物治疗的小鼠中，与仅接受CDDP治疗的小鼠相比，肿瘤生长相当快，尽管给予DFMO、MGBG和CDDP的动物肿瘤中的CDDP水平高于仅给予CDDP的动物。当给予DFMO、MGBG和CDDP或DFMO和MGBG时，肿瘤中的亚精胺和精胺水平明显降低。另一方面，仅接受CDDP治疗的组在治疗结束24小时后肿瘤DNA生物合成明显下降。这些结果表明，多胺缺乏引起的DNA结构改变可能会阻止CDDP在DNA中形成交联。