Colorectal Cancer
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 14, 2007; 13(10): 1534-1540
Published online Mar 14, 2007. doi: 10.3748/wjg.v13.i10.1534
Rosiglitazone enhances fluorouracil-induced apoptosis of HT-29 cells by activating peroxisome proliferator-activated receptor γ
Yan-Qin Zhang, Xiao-Qing Tang, Li Sun, Lin Dong, Yong Qin, Hua-Qing Liu, Hong Xia, Jian-Guo Cao
Yan-Qin Zhang, Li Sun, Lin Dong, Yong Qin, Hua-Qing Liu, Hong Xia, Jian-Guo Cao, Cancer Research Institute of Nanhua University, Hengyang 421001, Hunan Province, China
Xiao-Qing Tang, Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, Hunan Province, China
Author contributions: All authors contributed equally to the work.
Supported by National Natural Science Foundation of China, No. 30472040
Correspondence to: Professor Jian-Guo Cao, Cancer Research Institute of Nanhua University, Hengyang 421001, Hunan Province, China. caojianguo2005@yahoo.cn
Telephone: +86-734-8281510 Fax: +86-734-8281305
Received: November 28, 2006
Revised: January 17, 2007
Accepted: February 13, 2007
Published online: March 14, 2007
Abstract

AIM: To examine whether and how rosiglitazone enhances apoptosis induced by fluorouracil in human colon cancer (HT-29) cells.

METHODS: Human colon cancer HT-29 cells were cultured in vitro and treated with fluorouracil and/or rosiglitazone. Proliferation and growth of HT-29 cells were evaluated by MTT assay and trypan blue exclusion methods, respectively. The apoptosis of HT-29 cells was determined by acridine orange/ethidium bromide staining and flow cytometry using PI fluorescence staining. The expressions of peroxisome proliferator-activated receptor γ (PPARγ), Bcl-2 and Bax in HT-29 cells were analyzed by Western blot.

RESULTS: Although rosiglitazone at the concentration below 30 μmol/L for 72 h exerted almost no inhibitory effect on proliferation and growth of HT-29 cells, it could significantly enhance fluorouracil-induced HT-29 cell proliferation and growth inhibition. Furthermore, 10 μmol/L rosilitazone did not induce apoptosis of HT-29 cells but dramatically enhanced fluorouracil-induced apoptosis of HT-29 cells. However, rosiglitazone did not improve apoptosis induced by fluorouracil in HT-29 cells pretreated with GW9662, a PPARγ antagonist. Meanwhile, the expression of Bax and PPARγ was up-regulated, while the expression of Bcl-2 was down regulated in HT-29 cells treated with rosiglitazone in a time-dependent manner. However, the effect of rosiglitazone on Bcl-2 and Bax was blocked or diminished in the presence of GW9662.

CONCLUSION: Rosiglitazone enhances fluorouracil-induced apoptosis of HT-29 cells by activating PPARγ.

Keywords: Colon cancer; Rosiglitazone; Fluorouracil; Apoptosis