Matrine suppresses breast cancer cell proliferation and invasion via VEGF-Akt-NF-κB signaling
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Matrine has shown therapeutic and/or adjuvant therapeutic effects on the treatment of some patients with breast cancer. However, its mechanisms of action are largely unknown. To disclose the mechanisms, we investigated in vitro and ex vivo effects of matrine on the cancer cells. Our results confirmed that matrine significantly suppressed the proliferation of highly-metastatic human breast cancer MDA-MB-231 cell line. Matrine displayed synergistic effects with existing anticancer agents celecoxib (the inhibitor of cyclooxygenase-2), trichostatin A (the histone deacetylase inhibitor) and rosiglitazone against the proliferation and VEGF excretions in MDA-MB-231 cells. Matrine induced the apoptosis and cell cycle arrest by reducing the ratios of Bcl-2/Bax protein and mRNA levels in the cancer cells. Matrine significantly reduced the invasion, MMP-9/MMP-2 activation, Akt phosphorylation, nuclear factor κB p-65 expression and DNA binding activity, and mRNA levels of MMP-9, MMP-2, EGF and VEGFR1 in MDA-MB-231 cells. Collectively, our results suggest that matrine inhibits the cancer cell proliferation and invasion via EGF/VEGF-VEGFR1-Akt-NF-κB signaling pathway.
KeywordsMatrine Anticancer agents Human breast cancer Proliferation Invasion MMP-9/MMP-2 Akt signaling Nuclear factor κB
Vascular endothelial growth factor
Epidermal growth factor
Nuclear factor κB
Electrophoretic mobility shift assay
The authors would like to extend our thanks to Ronald E. Vincent (BIOCON Scientific) for his thoughtful reading and the help of Drs. Jianyuan Li and Shaohua Jin for FACS analysis. This work is supported in part by grants from the Ministry of Education of the People’s Republic of China to G.Z, from the Ministry of Human Resources and Social Security of the People’s Republic of China to G.Z, Projects of Yantai University to G.Z, and Projects from the Department of Science and Technology of Shandong Province to G.Z. (Y2008C71; 2009GG10002089).
- Gibson EM, Henson ES, Haney N, Villanueva J, Gibson SB (2002) Epidermal growth factor protects epithelial-derived cells from tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by inhibiting cytochrome c release. Cancer Res 62:488–496Google Scholar
- Koivunen E, Arap W, Valtanen H, Rainisalo A, Medina OP, Heikkila P, Kantor C, Gahmberg CG, Salo T, Konttinen YT, Sorsa T, Ruoslahti E, Pasqualini R (1999) Tumor targeting with a selective gelatinase inhibitor. Nat Biotechnol 1776:8–17774Google Scholar
- Marsden VS, O’Connor L, O’Reilly LA, Silke J, Metcalf D, Ekert PG, Huang DC, Cecconi F, Kuida K, Tomaselli KJ, Roy S, Nicholson DW, Vaux DL, Bouillet P, Adams JM, Strasser A (2002) Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome. Nature 419(6907):634–637CrossRefGoogle Scholar
- Park S, Bae J, Nam BH, Yoo KY (2008) Aetiology of cancer in Asia. Asian Pac J Cancer Prev 9:371–380Google Scholar
- Price JT, Tiganis T, Agarwal A, Djakiew D, Thompson EW (1999) Epidermal growth factor promotes MDA-MB-231 breast cancer cell migration through a phosphatidylinositol 3’-kinase and phospholipase C-dependent mechanism. Cancer Res 59:5475–5478Google Scholar