Colorectal Cancer
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jan 21, 2008; 14(3): 428-434
Published online Jan 21, 2008. doi: 10.3748/wjg.14.428
Inhibition of signal transducer and activator of transcription 3 expression by RNA interference suppresses invasion through inducing anoikis in human colon cancer cells
Yu Fan, You-Li Zhang, Ying Wu, Wei Zhang, Yin-Huan Wang, Zhao-Ming Cheng, Hua Li
Yu Fan, You-Li Zhang, Ying Wu, Wei Zhang, Yin-Huan Wang, Zhao-Ming Cheng, Department of Gastroenterology, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
Hua Li, Department of Pharmacology and Toxicology, Dartmouth Medical School, Dartmouth Medical School, Hanover, NH 03755, United States
Correspondence to: You-Li Zhang, Department of Gastroenterology, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China. zjyouli@yahoo.com.cn
Telephone: +86-511-85011787
Fax: +86-511-85026387
Received: June 30, 2007
Revised: October 29, 2007
Published online: January 21, 2008
Abstract

AIM: To investigate the roles and mechanism of signal transducer and activator of transcription 3 (STAT3) in invasion of human colon cancer cells by RNA interference.

METHODS: Small interfering RNA (siRNA) targeting Signal transducer and activator of transcription 3 (STAT3) was transfected into HT29 colon cancer cells. STAT3 protein level and DNA-binding activity of STAT3 was evaluated by western blotting and electrophoretic mobility shift assay (EMSA), respectively. We studied the anchorage-independent growth using colony formation in soft agar, and invasion using the boyden chamber model, anoikis using DNA fragmentation assay and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL), respectively. Western blot assay was used to observe the protein expression of Bcl-xL and survivin in colon cancer HT29 cells.

RESULTS: RNA interference (RNAi) mediated by siRNA leads to suppression of STAT3 expression in colon cancer cell lines. Suppression of STAT3 expression by siRNA could inhibit anchorage-independent growth, and invasion ability, and induces anoikis in the colon cancer cell line HT29. It has been shown that knockdown of STAT3 expression by siRNA results in a reduction in expression of Bcl-xL and survivin in HT29 cells.

CONCLUSION: These results suggest that STAT3 siRNA can inhibit the invasion ability of colon cancer cells through inducing anoikis, which antiapoptotic genes survivin and Bcl-xL contribute to regulation of anoikis. These studies indicate STAT3 siRNA could be a useful therapeutic tool for the treatment of colon cancer.

Keywords: Colon cancer; Invasion; Signal transducer and activator of transcription 3; Anoikis