Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2015; 21(9): 2645-2650
Published online Mar 7, 2015. doi: 10.3748/wjg.v21.i9.2645
Angiopoietin and vascular endothelial growth factor expression in colorectal disease models
Wei-Xin Liu, Shou-Zhi Gu, Shen Zhang, Yi Ren, Li-Xuan Sang, Cong Dai
Wei-Xin Liu, Shen Zhang, Yi Ren, Li-Xuan Sang, Cong Dai, Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China
Shou-Zhi Gu, Department of Anatomy, Seirei Christopher College, Hamamatsu 433-8558, Japan
Author contributions: Liu WX and Gu SZ designed the research; Zhang S, Ren Y, Sang LX and Dai C performed the research; Liu WX, Gu SZ and Dai C analyzed the data; Liu WX and Gu SZ wrote the paper.
Supported by Science and Technology Project of Liaoning Province, No. 2013225303; and the Science and Technology Project of Shenyang City, No. F13-316-1-40.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Wei-Xin Liu, Professor, Department of Gastroenterology, First Affiliated Hospital, China Medical University, No. 155 North Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, China. weixinliu@yahoo.com
Telephone: +86-24-83282863 Fax: +86-24-83282863
Received: September 20, 2014
Peer-review started: September 21, 2014
First decision: October 14, 2014
Revised: November 6, 2014
Accepted: December 5, 2014
Article in press: December 8, 2014
Published online: March 7, 2015
Processing time: 169 Days and 17.5 Hours
Abstract

AIM: To investigate angiopoietin (Ang) and vascular endothelial growth factor (VEGF) expression in rats with ulcerative colitis (UC) and colorectal cancer (CRC).

METHODS: Dysplasia and cancer were investigated in rats that received three cycles of 3.5% dextran sulfate sodium (DSS) in drinking water for 7 d followed by distilled water for 14 d after intraperitoneal pretreatment with 20 mg/kg 1,2-dimethylhydrazine (DMH) (CRC group). Colitis was investigated in rats that received three cycles of 3.5% DSS in drinking water for 7 d followed by distilled water for 14 d after intraperitoneal pretreatment with saline (UC group). Rats without DSS or DMH treatment served as controls. Expression of the tyrosine kinase with immunoglobulin-like and EGF-like domains (Tie)-2 and its ligands, Ang-1 and Ang-2, as well as VEGF were evaluated in the colorectum by Western blotting.

RESULTS: Compared with rats in the control group, rats in the CRC and UC groups developed the symptoms of acute colitis with diarrhea, rectal bleeding, wasting, and loss of body weight (P < 0.05). In addition, the mean length of colorectum of CRC and UC rats was significantly shorter than that of control rats (8.29 ± 0.21 and 8.31 ± 0.86, respectively, vs 12.34 ± 0.12 cm; P < 0.05). Furthermore, rats in the CRC group, but not in the UC or control groups, developed multiple tumors in the colorectal region. Western blot analysis revealed that rats in the CRC and UC groups had markedly increased protein levels of Ang-1, Ang-2, Tie-2, and VEGF in the colorectum compared to rats in the control group.

CONCLUSION: Increased expression of Ang-1, Ang-2, Tie-2, and VEGF in ulcerative colitis-derived colorectal cancer might lead to chronic colitis and pathologic angiogenesis in rats.

Keywords: Angiopoietin-1; Angiopoietin-2; Colorectal cancer; Tie-2; Ulcerative colitis; Vascular endothelial growth factor

Core tip: Colorectal cancer is the most severe complication in ulcerative colitis. Angiopoietin (Ang)-1, Ang-2, their receptor, tyrosine kinase with immunoglobulin-like and EGF-like domains (Tie)-2, and vascular endothelial growth factor may play a key role in forming vasculature which is involved in carcinogenesis. In this study, rats with ulcerative colitis and colorectal cancer had increased expression of these proteins, which suggests they may contribute to the development of colon cancer, chronic colitis, and pathologic angiogenesis in the rat.