Dual down-regulation of EGFR and ErbB2 by berberine contributes to suppression of migration and invasion of human ovarian cancer cells
Autor: | Shih Chung Hsu, Han Peng Kuo, Tzu-Chao Chuang, Shou Lun Lee, Ming-Ching Kao, Kuohui Wu, Vinchi Wang, Ying Yu Lin |
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Rok vydání: | 2020 |
Předmět: |
Berberine
Receptor ErbB-2 Health Toxicology and Mutagenesis Motility Down-Regulation 010501 environmental sciences Management Monitoring Policy and Law Matrix metalloproteinase Toxicology 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Phosphatidylinositol 3-Kinases 0302 clinical medicine Cyclin D1 Downregulation and upregulation Cell Line Tumor medicine Humans skin and connective tissue diseases neoplasms PI3K/AKT/mTOR pathway 0105 earth and related environmental sciences Ovarian Neoplasms Akt/PKB signaling pathway General Medicine medicine.disease ErbB Receptors chemistry 030220 oncology & carcinogenesis Cancer research Female Ovarian cancer |
Zdroj: | Environmental toxicologyREFERENCES. 36(5) |
ISSN: | 1522-7278 |
Popis: | The overexpression of EGFR and/or ErbB2 occurs frequently in ovarian cancers and is associated with poor prognosis. The purpose of this study was to examine the anticancer effects and molecular mechanisms of berberine on human ovarian cancer cells with different levels of EGFR and/or ErbB2. We found that berberine reduced the motility and invasiveness of ovarian cancer cells. Berberine depleted both EGFR and ErbB2 in ovarian cancer cells. Furthermore, berberine suppressed the activation of the EGFR and ErbB2 downstream targets cyclin D1, MMPs, and VEGF by down-regulating the EGFR-ErbB2/PI3K/Akt signaling pathway. The berberine-mediated inhibition of MMP-2 and MMP-9 activity could be rescued by co-treatment with EGF. Finally, we demonstrated that berberine induced ErbB2 depletion through ubiquitin-mediated proteasome degradation. In conclusion, the suppressive effects of berberine on the ovarian cancer cells that differ in the expression of EGFR and ErbB2 may be mediated by the dual depletion of EGFR and/or ErbB2. |
Databáze: | OpenAIRE |
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