COX-2/PGE2 regulates VEGF expression by activating wnt/β-catenin signal pathway in human colorectal cancer cells
10.3724/SP.J.1008.2012.01178
- Author:
Xuan LIU
1
Author Information
1. Department of Oncology, Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine
- Publication Type:Journal Article
- Keywords:
Colorectal neoplasms;
Cyclooxygenase 2;
Vascular endothelial growth factor;
Wnt/β-catenin signal pathway
- From:
Academic Journal of Second Military Medical University
2012;33(11):1178-1181
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate whether COX-2/PGE2 can regulate vascular endothelial growth factor (VEGF) expression through activating Wnt/β-catenin signal pathway in human colorectal cancer cells. Methods: PGE2 and (or) COX-2 selective inhibitor NS-398 was used to treat LoVo cells for 24 h, and then COX-2 and β-catenin protein expression was detected by Western blotting analysis. PGE2 and (or) β-catenin/tcf selective inhibitor FH-535 were used to treat LoVo cells for 24 h, and then the levels of VEGF was determined by ELISA. Routinely cultured LoVo cells were taken as control. Results: Compared with the control group, PGE2 not only increased COX-2 protein expression, but also increased the levels of β-catenin in the total cell, cytosolic and nuclear proteins (being 3. 8 folds, 2. 7 folds, and 3. 0 folds of the control, respectively, P< 0. 01). COX-2 selective inhibitor not only decreased COX-2 protein expression, but also decreased the levels of β-catenin in the total cell, cytosolic and nuclear proteins (being 0. 3 folds, 0. 3 folds, and 0. 2 folds of the control, P<0. 01). Compared with the control group, PGE2 increased VEGF expression in LoVo cells (being 1. 6 folds of the control, P<0. 01), and β-catenin/tcf selective inhibitor decreased VEGF expression in LoVo cells (being 0. 68 folds of the control, P<0. 01). Co-treatment of LoVo cells with β-catenin/tcf selective inhibitor and PGE2 showed no great effect on VEGF expression. Conclusion: COX-2/PGE2 can β-catenin protein level, subsequently activate Wnt/p-catenin signal pathway and promote VEGF expression, which increase might be one of the mechanisms for COX-2/PGE2-induced angiogenesis in colon cancer.
