Colorectal Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 7, 2006; 12(45): 7263-7270
Published online Dec 7, 2006. doi: 10.3748/wjg.v12.i45.7263
Effect of ligand troglitazone on peroxisome proliferator-activated receptor γ expression and cellular growth in human colon cancer cells
Mei Ming, Jie-Ping Yu, Xiang-Zhi Meng, Yan-Hong Zhou, Hong-Gang Yu, He-Sheng Luo
Mei Ming, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Mei Ming, Department of Pathophysiology and Pathology, Medical College of Wuhan University, Wuhan 430071, Hubei Province, China
Jie-Ping Yu, Yan-Hong Zhou, Hong-Gang Yu, He-Sheng Luo, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Xiang-Zhi Meng, Department of Pathophysiology and Pathology, Medical College of Wuhan University, Wuhan 430071, Hubei Province, China
Correspondence to: Hong-Gang Yu, Department of Gastro-enterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China. stillwatermm@163.com
Telephone: +86-27-63540075 Fax: +86-27-68758593
Received: October 5, 2006
Revised: October 28, 2006
Accepted: November 9, 2006
Published online: December 7, 2006
Abstract

AIM: To investigate the effect of troglitazone on pe-roxisome proliferator-activated receptor γ (PPARγ) expression and cellular growth in human colon cancer HCT-116 and HCT-15 cells and to explore the related molecular mechanism.

METHODS: Human colon cancer HCT-116 and HCT-15 cells cultured in vitro were treated with troglitazone. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were employed to detect the effect of troglitazone on PPARγ expression. The proliferative activity was determined by MTT assay, cell cycle and apoptosis were detected by flow cytometry. Apoptosis-related genes, cell cycle regulatory genes and p53 were examined by RT-PCR and Western blot respectively.

RESULTS: The expression of PPARγ in colon cancer HCT-116 and HCT-15 cells was up-regulated by troglitazone. Troglitazone inhibited proliferation, induced apoptosis and cell cycle G1 arrest in colon cancer cells. Troglitazone induced p53 expression in HCT-116 cells, but not in HCT-15 cells. The down-regulation of survivin and bcl-2 was found in both cell lines and up-regulation of bax was found only in HCT-116 cells, being consistent with growth inhibition in HCT-116 cells but not in HCT-15 cells. Troglitazone increased expression of p21WAF1/CIP1 (p21), p27KIP1 (p27) and reduced cyclin D1 in HCT-116 cells while only a minor decrease of cyclin D1 was found in HCT-15 cells.

CONCLUSION: Troglitazone is an inductor of PPARγ in colon cancer cells and inhibits PPARγ-dependently proliferation, which may attribute to cell cycle G1 arrest and apoptosis in colon cancer cells. Troglitazone may induce p53-independent apoptosis and p53-dependent expression of p21 and p27. Depending on cell background, different activation pathways may exist in colon cancer cells.

Keywords: Peroxisome proliferator-activated receptor γ; Colon cancer; Troglitazone; Cellular growth; Cell cycle; Apoptosis