Stat3 is involved in angiotensin II-induced expression of MMP2 in gastric cancer cells.
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.
Huang
Wei
W
Department of Gastroenterology, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai 200025, China.
Yu
Li-Fen
LF
Zhong
Jie
J
Wu
Wei
W
Zhu
Jia-Ying
JY
Jiang
Feng-Xiang
FX
Wu
Yun-Lin
YL
D000804:Angiotensin II / Q000502:physiology*; D015153:Blotting, Western; D002470:Cell Survival; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D020032:Tyrphostins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D020032:Tyrphostins; D042461:Vascular Endothelial Growth Factor A; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D000804:Angiotensin II; D020778:Matrix Metalloproteinase 2