Saydjari R, Alexander R W, Upp J R, Barranco S C, Townsend C M, Thompson J C
Department of Surgery, University of Texas Medical Branch, Galveston 77550.
Int J Cancer. 1991 Jan 2;47(1):44-8. doi: 10.1002/ijc.2910470109.
Polyamines are essential for normal and neoplastic growth. Ornithine decarboxylase (ODC) is the first and rate-limiting enzyme in the polyamine biosynthetic pathway. alpha-Difluoromethylornithine (DFMO) is an enzyme-activated irreversible inhibitor of ODC, and a known anti-neoplastic agent. The purpose of this study was to examine the susceptibility of various human cancers to inhibition by DFMO in vivo. We have studied three human pancreatic adenocarcinomas, designated CAV, SKI, and PGER, two human colon adenocarcinomas (LS-180 and WIDR), and three metastatic cell lines of a human gastric adenocarcinoma (BHM, BMM, BLM) that were growing in congenitally athymic (nude) Balb/c mice. Mice bearing each tumor were divided into two groups; one group served as controls and the other group received DFMO 3% in drinking water. Tumor growth and weight, and content of DNA, RNA, protein and polyamines were determined and correlated. DFMO significantly inhibited the growth of three of the three gastric tumors, two of the three pancreatic tumors and neither of the two colon tumors. The tumor content of DNA, RNA and protein exhibited a pattern that was parallel to tumor growth. The tumor polyamine concentration did not correlate with sensitivity to DFMO. These findings provide clear evidence for important differences in the sensitivity of various human cancers to growth inhibition by DFMO and indicate that endogenous polyamine levels alone do not predict the sensitivity of the tumors to DFMO.
多胺对于正常生长和肿瘤生长至关重要。鸟氨酸脱羧酶（ODC）是多胺生物合成途径中的首个限速酶。α-二氟甲基鸟氨酸（DFMO）是一种酶激活的ODC不可逆抑制剂，也是一种已知的抗肿瘤药物。本研究的目的是检测各种人类癌症在体内对DFMO抑制作用的敏感性。我们研究了三种人类胰腺腺癌，分别命名为CAV、SKI和PGER，两种人类结肠腺癌（LS-180和WIDR），以及三种在先天性无胸腺（裸）Balb/c小鼠体内生长的人类胃腺癌转移细胞系（BHM、BMM、BLM）。携带每种肿瘤的小鼠被分为两组；一组作为对照组，另一组饮用含3% DFMO的水。测定并关联了肿瘤生长、重量以及DNA、RNA、蛋白质和多胺的含量。DFMO显著抑制了三种胃肿瘤中的三种、三种胰腺肿瘤中的两种，而对两种结肠肿瘤均无抑制作用。DNA、RNA和蛋白质的肿瘤含量呈现出与肿瘤生长平行的模式。肿瘤多胺浓度与对DFMO的敏感性无关。这些发现为各种人类癌症对DFMO生长抑制的敏感性存在重要差异提供了明确证据，并表明仅内源性多胺水平不能预测肿瘤对DFMO的敏感性。
