Matrine suppresses breast cancer cell proliferation and invasion via VEGF-Akt-NF-κB signaling

被引:162
作者
Yu, Pengfei [1 ]
Liu, Qian [1 ]
Liu, Kun [1 ]
Yagasaki, Kazumi [2 ]
Wu, Erxi [3 ]
Zhang, Guoying [1 ]
机构
[1] Yantai Univ, Mol Pharmacol Lab, Sch Pharm, Yantai 264005, Shandong, Peoples R China
[2] Tokyo Noko Univ, Dept Appl Biol Sci, Fuchu, Tokyo 1838509, Japan
[3] N Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58105 USA
关键词
Matrine; Anticancer agents; Human breast cancer; Proliferation; Invasion; MMP-9/MMP-2; Akt signaling; Nuclear factor kappa B; BCL-2-RELATED PROTEINS; IN-VIVO; EXPRESSION; APOPTOSIS; MIGRATION; MMP-9; INVASIVENESS; METASTASIS; ACTIVATION; INHIBITOR;
D O I
10.1007/s10616-009-9225-9
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 kappa B 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-kappa B signaling pathway.
引用
收藏
页码:219 / 229
页数:11
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