Inhibitory effects of tetrandrine on epidermal growth factor-induced invasion and migration in HT29 human colorectal adenocarcinoma cells

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Publisher： Spandidos Publications

E-ISSN： 1791-3004|13|1|1003-1009

ISSN： 1791-2997

Source： Molecular Medicine Reports, Vol.13, Iss.1, 2016-01, pp. : 1003-1009

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Abstract

Tetrandrine has been shown to reduce cancer cell proliferation and to inhibit metastatic effects in multiple cancer models in vitro and in vivo. However, the effects of tetrandrine on the underlying mechanism of HT29 human colorectal adenocarcinoma cell metastasis remain to be fully elucidated. The aim of the present study was focused on tetrandrinetreated HT29 cells following epidermal growth factor (EGF) treatment, and Transwell, gelatin zymography, gene expression and immunoblotting assays were performed to investigate metastatic effects in vitro. Tetrandrine was observed to dosedependently inhibit EGFinduced HT29 cell invasion and migration, however, no effect on cell viability occurred following exposure to tetradrine between 0.5 and 2 µM. Tetrandrine treatment inhibited the enzymatic activity of matrix metalloprotease (MMP)2 and MMP9 in a concentrationdependent manner. The present study also found a reduction in the mRNA expression levels of MMP2 and MMP9 in the tetrandrinetreated HT29 cells. Tetrandrine also suppressed the phosphorylation of EGF receptor (EGFR) and its downstream pathway, including phosphoinositidedependent kinase 1, phosphatidylinositol 3kinase and phosphorylated AKT, suppressing the gene expression of MMP2 and MMP9. Furthermore, tetrandrine triggered mitogenactivated protein kinase signaling through the suppressing the activation of phosphorylated extracellular signalregulated protein kinase. These data suggested that targeting EGFR signaling and its downstream molecules contributed to the inhibition of EGFinduced HT29 cell metastasis caused by tetrandrine, eventually leading to a reduction in the mRNA and gelatinase activities of MMP-2 and MMP-9, respectively.