Inhibitory effects of tetrandrine on epidermal growth factor-induced invasion and migration in HT29 human colorectal adenocarcinoma cells
| Autor: | Jai Sing Yang, Ni Na Chiang, Jo Hua Chiang, Chiu Fang Lee, Chi Cheng Lu, Chi‑Ting Horng, Fu‑An Chen |
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| Rok vydání: | 2014 |
| Předmět: |
0301 basic medicine
Cancer Research Cell Biology Adenocarcinoma Biochemistry Benzylisoquinolines 03 medical and health sciences chemistry.chemical_compound Phosphatidylinositol 3-Kinases 0302 clinical medicine Epidermal growth factor Cell Movement Genetics medicine Humans Neoplasm Invasiveness Protein kinase A Molecular Biology Cell Proliferation Epidermal Growth Factor Cell growth Kinase Cell cycle Cell biology Tetrandrine ErbB Receptors Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure Oncology chemistry Matrix Metalloproteinase 9 030220 oncology & carcinogenesis Molecular Medicine Matrix Metalloproteinase 2 Signal transduction Colorectal Neoplasms HT29 Cells Signal Transduction |
| Zdroj: | Molecular medicine reports. 13(1) |
| ISSN: | 1791-3004 |
| Popis: | 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 tetrandrine‑treated 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 dose‑dependently inhibit EGF‑induced 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 MMP‑9 in a concentration‑dependent manner. The present study also found a reduction in the mRNA expression levels of MMP‑2 and MMP‑9 in the tetrandrine‑treated HT29 cells. Tetrandrine also suppressed the phosphorylation of EGF receptor (EGFR) and its downstream pathway, including phosphoinositide‑dependent kinase 1, phosphatidylinositol 3‑kinase and phosphorylated AKT, suppressing the gene expression of MMP‑2 and MMP‑9. Furthermore, tetrandrine triggered mitogen‑activated protein kinase signaling through the suppressing the activation of phosphorylated extracellular signal‑regulated protein kinase. These data suggested that targeting EGFR signaling and its downstream molecules contributed to the inhibition of EGF‑induced HT29 cell metastasis caused by tetrandrine, eventually leading to a reduction in the mRNA and gelatinase activities of MMP-2 and MMP-9, respectively. |
| Databáze: | OpenAIRE |
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