P017 Periostin aggravates the development of colitis-associated colon cancer in mice
S.-J. Koh*1, J. W. Kim1, B. G. Kim1, K. L. Lee1, J. S. Kim2
1Seoul National University Boramae Hospital, Seoul National University College of Medicine, Internal Medicine, Seoul, South Korea, 2Seoul National University College of Medicine, Internal Medicine and Liver Research Institute, Seoul, South Korea
Periostin is a matricellular protein that interacts with various integrin molecules on the cell surface. Although periostin is expressed in inflamed colonic mucosa and colon cancer, its role in the colitis-associated colon cancer remains unclear.
Wild-type and Postn-/- mice were given a single intraperitoneal injection of azoxymethane (AOM, 12.5 mg/kg) on Day 0; 7 days later, 2% dextran sulfate sodium (DSS) was administered via drinking water for 5 days, followed by free water consumption for 16 days. This cycle was repeated 3 times. Immunohistochemical staining for phospho-IκB kinase (IKK) and β-catenin, and in-situ TUNEL assay were performed in mouse colon tissue. In-vitro assays were performed using COLO205 cells. Small interfering RNA was used to inhibit Postn gene.
Postn-/- mice exhibited lower tumour burden compared with wild-type mice. Exposure to AOM/DSS resulted in extensive epithelial apoptosis in Postn-/- mice compared with wild-type mice. In addition, immunoreactivity for IKK and β-catenin was markedly reduced in Postn-/- mice. Silencing of Postn gene resulted in reduced cell proliferation in COLO205 cells. Silencing of Postn downregulated the expression of BcL-2, cIAP1, cFLIP-L, and VEGF and upregulated the expression of Bak. In addition, the expression of β-catenin-downstream genes, such as axin2 and cyclin D1 were suppressed by the knockdown of Postn gene.
Periostin aggravates the development of colitis-associated colon cancer, which suggests that periostin is a potential therapeutic target for the prevention of colon cancer in inflammatory bowel disease.