期刊
CHINESE JOURNAL OF CANCER RESEARCH
卷 24, 期 2, 页码 116-123出版社
SPRINGER
DOI: 10.1007/s11670-012-0116-9
关键词
Colorectal neoplasms; Drug resistance; Glycogen synthase kinase 3 beta; Fluorouracil; beta-catenin; E2F-1
类别
资金
- Sci-Tech Project Foundation of Guangdong Province [2009B080800023]
To explore the effects and mechanism of glycogen synthase kinase 3 beta (GSK-3 beta) inhibitor (2'Z,3'E)-6-bromo-indirubin-3'-oxime (BIO) on drug resistance in colon cancer cells. The colon cancer SW480 and SW620 cells were treated with BIO, 5-fluorouracil (5-FU) and BIO/5-FU, separately. Cell cycle distribution, apoptosis level and efflux ability of rhodamine 123 (Rh123) were detected by flow cytometry. The protein expressions of P-glycoprotein (P-gp), multidrug resistance protein 2 (MRP2), thymidylate synthase (TS), beta-catenin, E2F-1 and Bcl-2 were detected by Western blot. beta-catenin and P-gp were stained with double immunofluorescence and observed under a confocal microscope. BIO up-regulated beta-catenin, P-gp, MRP2 and TS, enhanced the efflux ability of Rh123, decreased Bcl-2 protein and gave the opposite effect to E2F-1 protein in SW480 and SW620 cells. Furthermore, BIO significantly inhibited cell apoptosis, increased S and G(2)/M phase cells, and reduced the cell apoptosis induced by 5-FU in SW480 cells, whereas the effects were slight or not obvious in SW620 cells. GSK-3 beta was involved in drug resistance regulation, and activation of beta-catenin and inhibition of E2F-1 may be the most responsible for the enhancement of 5-FU chemotherapy resistance induced by GSK-3 beta inhibitor BIO in colon cancer.
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