- 作者：Meng-Chiu Lin ; Shu-Yao Tsai ; Fu-Yu Wang ; Fu-Hsuan Liu ; Jia-Ning Syu ; Feng-Yao Tang
- 关键词：Akt ; human colon cancer cells ; invasion ; leptin ; MAPK ; matrilysin ; siRNA
- 刊名：BioMedicine
- 出版年：December, 2013
- 年：2013
- 卷：3
- 期：4
- 页码：174-180
- 全文大小：696 K
Objective
To investigate the effects of leptin on matrix metalloproteinase-7 (MMP-7) expression and cellular invasion of human colon cancer cells.Methods
Human colon cancer cells were stimulated with leptin at various concentrations (0聽nM, 1.2聽nM, 6聽nM, 25聽nM, and 100聽nM), and the stimulatory effects of leptin on the invasion of human colon cancer cells were tested by the transwell invasion assay. The effects of leptin on signaling cascade in colon cancer cells were examined by Western blot assay and zymogram analysis.
Results
This study demonstrated that leptin dose-dependently induced MMP-7 expression and cellular invasion of human colon cancer HT-29 cells. Treatment of MMP-7 small interfering RNA (siRNA) significantly blocked leptin-mediated cellular invasion. Wortmannin [a聽phosphoinositide-3-kinase (PI3K) specific inhibitor], PD098059 (a Mitogen-activated protein kinases (MAPK)/ extracellular signal-regulated kinase (ERK) kinase (MEK) specific inhibitor), or GM-6001 (a specific inhibitor of MMPs) could suppress leptin-mediated cellular invasion markedly. These aver leptin inducing MMP-7 expression and/or cellular invasion, partly by modulation of phosphoinositide-3-kinase (PI3K)/ AKT and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway in human colon cancer HT-29 cells.
Conclusion
Results suggest a novel mechanism of leptin involved in MMP-7 expression and cellular invasion in human colon cancer HT-29 cells.