Stat3 Is Involved in Angiotensin II-Induced Expression of MMP2 in Gastric Cancer Cells

• Published in: Digestive diseases and sciences Vol. 54; no. 10; pp. 2056 - 2062
• Main Authors: Huang, Wei, Yu, Li-Fen, Zhong, Jie, Wu, Wei, Zhu, Jia-Ying, Jiang, Feng-Xiang, Wu, Yun-Lin
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.10.2009; Springer US; Springer; Springer Nature B.V
• Subjects: Angiotensin II - physiology; Biochemistry; Biological and medical sciences; Blotting, Western; Cell Survival; Chromatin Immunoprecipitation; Electrophoretic Mobility Shift Assay; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Hepatology; Humans; Matrix Metalloproteinase 2 - analysis; Medical sciences; Medicine; Medicine & Public Health; Oncology; Original Article; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Signal Transduction - physiology; STAT3 Transcription Factor - physiology; Stomach Neoplasms - metabolism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Transplant Surgery; Tumor Cells, Cultured; Tumors; Tyrphostins - pharmacology; Vascular Endothelial Growth Factor A - analysis; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Stat3; Angiotensin II; Gastric cancer; MMP2; Peptide hormone; Metabolic diseases; Malignant tumor; Stomach cancer; Octapeptide; Transcription factor STAT3; Gastroenterology; Digestive diseases; Tumor cell; Cancer; Gastric disease
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-008-0617-z

The expression of matrix metalloproteinase-2 (MMP2) has been linked with tumor invasion, angiogenesis, and metastasis. It has been reported that angiotensin II (Ang II) can induce MMP2 expression in gastric cancer cells. However, the molecular basis for Ang II regulates MMP2 expression in gastric cancer cells remains unclear. The aim of our study is to explore whether angiotensin II could induce MMP2 expression mediated through the Stat signaling pathway and its potential mechanism. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-binding assays was employed to determine the DNA-STAT binding activity. MMP2 and VEGF expression was analyzed with real-time PCR and Western blots. To examine the role of Stat3 in angiotensin II-induced MMP2 expression, A JAK-specific inhibitor and AG490 were used. Angiotensin II activated STAT-DNA binding activity in dose-dependent manners in gastric cancer cells. AG490 markedly inhibited angiotensin II-induced Stat3 activation and the expression of MMP2 and VEGF in gastric cancer cells. These results indicate that Stat3 may at least in part mediate angiotensin II-induced MMP2 mRNA expression in human gastric cancer cells. The activation of the JAK/Stat3 signaling pathway plays an important role in the progression of gastric cancer and that blockade of JAK/Stat3 signals may provide a novel therapeutic strategy for gastric cancer.