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添加 2-脱氧葡萄糖可增强二甲双胍处理的结肠癌细胞的生长抑制作用,但可逆转其酸化。

Addition of 2-deoxyglucose enhances growth inhibition but reverses acidification in colon cancer cells treated with phenformin.

机构信息

Department of Biochemistry and Molecular Biology, UMDNJ - New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.

出版信息

Anticancer Res. 2011 Feb;31(2):421-6.

PMID:21378320
Abstract

A report that effects of butyrate on some cells may be mediated by activation of AMP-activated protein kinase (AMPK) prompted this study which examines if other AMPK activators can induce differentiation and inhibit proliferation of colon cancer cells in a manner similar to butyrate. Using induction of alkaline phosphatase as a marker, it was observed that compound C, an AMPK inhibitor, is able to reduce the differentiating effect of butyrate on SW1116 and Caco-2 colon cancer cells. Metformin was observed to be less effective than butyrate in the induction of alkaline phosphatase but was more effective as a growth inhibitor. Phenformin was found to be a more potent growth inhibitor than metformin and both compounds cause acidification of the medium when incubated with colon cancer cells. Combined incubation of 2-deoxyglucose with either of the biguanides prevented the acidification of the medium but enhanced the growth inhibitory effects.

摘要

一份报告指出,丁酸盐对某些细胞的作用可能是通过激活 AMP 激活的蛋白激酶(AMPK)介导的,这促使本研究探讨其他 AMPK 激活剂是否可以以类似于丁酸盐的方式诱导结肠癌细胞分化和抑制增殖。使用碱性磷酸酶的诱导作为标记,观察到 AMPK 抑制剂化合物 C 能够降低丁酸盐对 SW1116 和 Caco-2 结肠癌细胞的分化作用。二甲双胍在诱导碱性磷酸酶方面的效果不如丁酸盐,但作为生长抑制剂的效果更好。苯乙双胍被发现比二甲双胍更能抑制细胞生长,并且这两种化合物在与结肠癌细胞孵育时都会导致培养基酸化。与双胍类药物之一联合孵育 2-脱氧葡萄糖可防止培养基酸化,但增强了生长抑制作用。

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