期刊
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
卷 301, 期 2, 页码 625-630出版社
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.301.2.625
关键词
-
Differentiation of human colonic cancer cells at confluency has been correlated to their increased resistance to chemotherapeutic agents. The aim of this study was to determine whether blocking Caco-2 cell differentiation could sensitize the cells to 5-fluorouracil (5-FU) treatment. We show that in cells at confluency, geraniol (400 muM) prevented the formation of brush-border membranes and inhibited the expression of intestinal hydrolases (sucrase, lactase, alkaline phosphatase). The anti-proliferative effect of geraniol (400 muM) together with 5-FU (5 muM) was twice that of 5-FU alone. The cytotoxicity induced by 5-FU was enhanced in the presence of geraniol, as shown by a 50% increase of lactate dehydrogenase release in the culture medium. These effects are related to enhanced intracellular accumulation of 5-FU in the presence of geraniol as shown by a 2-fold increase in intracellular 5-[6-H-3]FU (1.5 muCi/ml). It is concluded that geraniol sensitizes colonic cancer cells to 5- FU treatment, by increasing the cytotoxicity of the drug, and that this results from the facilitated transport of 5-FU and the blockade of the morphological and functional differentiation of the cancer cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据