Antimetastatic activity of DL-alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, in mice.
Antimetastatic activity of DL-alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, in mice.
复制标题
DL-α-二氟甲基鸟氨酸（一种多胺生物合成抑制剂）在小鼠中的抗转移活性。
作者：
P. Sunkara;A. Rosenberger
我们早期的研究表明，多胺（即腐胺，亚精胺和精胺）不仅在肿瘤生长中，而且在肿瘤转移中的作用。我们已经观察到，α-二氟甲基鸟氨酸（DFMO），一种不可逆的鸟氨酸脱羧酶抑制剂的管理，导致在植入刘易斯肺癌小鼠的视觉可检测的肺转移显着抑制。本研究的目的是研究DFMO对其他自发性和实验性转移模型的影响，并确定肿瘤转移级联反应中的哪些步骤对DFMO敏感。在本研究中，恶性小鼠B16无黑色素性黑色素瘤（B16 a）的结果显示，DFMO对肿瘤生长和肉眼可检测的肺转移的抑制具有剂量依赖性作用。DFMO以0.5%、1%和2%的饮用水溶液给药时，分别导致0、24.5%和60%的肿瘤生长抑制，而在相同剂量下，观察到55%、83%和96%的可见转移抑制。在1%和2% DFMO的处理水平下，30%和65%的动物无转移。0.5%的DFMO对肿瘤生长没有任何影响，而观察到对可见肺转移的显著55%抑制，表明多胺在肿瘤转移中的特定作用。DFMO治疗还导致肿瘤组织中腐胺和亚精胺水平显著降低，精胺浓度略有增加。DFMO给药不抑制由于将B16黑色素瘤（F10系）肿瘤和刘易斯肺癌细胞静脉注射到尾静脉中而诱导的实验转移。这些结果提供了初步证据，表明DFMO引起的肿瘤细胞多胺耗竭可能影响转移级联反应的第一步，即内渗（即，防止转移性肿瘤细胞侵入血管或血管），尽管不能排除DFMO对转移级联中其他步骤的影响。
Our earlier studies indicated a role for polyamines (namely, putrescine, spermidine, and spermine) not only in tumor growth but also in tumor metastases. We have observed that administration of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, resulted in significant inhibition of visually detectable pulmonary metastases in mice implanted with Lewis lung carcinoma. The objective of the present study is to investigate the effect of DFMO on other spontaneous and experimental metastatic models and also to determine which step(s) in the tumor metastatic cascade is sensitive to DFMO. The results presented in this study with malignant mouse B16 amelanotic melanoma (B16a) showed a dose-dependent effect of DFMO on the inhibition of both tumor growth and grossly detectable pulmonary metastases. DFMO, when administered as 0.5, 1, and 2% solution in drinking water, resulted in 0, 24.5, and 60% inhibition of tumor growth, respectively, whereas at the same doses an inhibition of 55, 83, and 96% of visible metastases was observed. At treatment levels of 1 and 2% DFMO, 30 and 65% of the animals were free of metastases. DFMO, at 0.5%, did not show any effect on tumor growth, while a significant 55% inhibition of visible pulmonary metastasis was observed, suggesting a specific role for polyamines in tumor metastasis. DFMO treatment also resulted in a significant reduction of putrescine and spermidine levels with a slight increase in spermine concentration in the tumor tissue. DFMO administration did not inhibit the experimental metastases induced as a result of i.v. injection of B16 melanoma (line F10) tumor and Lewis lung carcinoma cells into the tail vein. These results provide preliminary evidence to indicate that tumor cell polyamine depletion by DFMO might affect the first step in the metastatic cascade, intravasation (i.e., prevent the invasion of metastatic tumor cells into lymphatics or blood vessels), although the effect of DFMO on other steps in the metastatic cascade cannot be ruled out.
通过 D,L-α-二氟甲基鸟氨酸处理消除 9L 大鼠脑肿瘤细胞多胺含量，抑制增殖和 G1 到 S 的转变。
影响因子：
3.7
作者：
Seidenfeld,J;Gray,JW;Marton,LJ
通讯作者：
Marton,LJ
α-二氟甲基鸟氨酸（一种鸟氨酸脱羧酶抑制剂）增强 1,3-双（2-氯乙基）-1-亚硝基脲的抗肿瘤治疗作用。
影响因子：
11.2
作者：
Marton,LJ;Levin,VA;Hervatin,SJ;Koch-Weser,J;McCann,PP;Sjoerdsma,A
通讯作者：
Sjoerdsma,A
使用 DL-α-二氟甲基鸟氨酸成功治疗无胸腺小鼠体内的人小细胞变异型肺癌植入物。
影响因子：
11.2
作者：
Luk,GD;Abeloff,MD;Griffin,CA;Baylin,SB
通讯作者：
Baylin,SB