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

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Abstract

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.

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Abbreviations

MA:

Matrine

T:

Trichostatin A

LY:

Ly294002

Bay:

Bay 11-7082

S:

Celecoxib

KA:

Carmofur

NA:

Navelbine

Ro:

Rosiglitazone

LO:

Lovastatin

VEGF:

Vascular endothelial growth factor

VEGFR1:

VEGF receptor-1

EGF:

Epidermal growth factor

pro-MMP-9:

Pro-matrix metalloproteinase-9

pro-MMP-2:

Pro-matrix metalloproteinase-2

NF-κB:

Nuclear factor κB

EMSA:

Electrophoretic mobility shift assay

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Acknowledgments

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).

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Authors and Affiliations

  1. Laboratory of Molecular Pharmacology, School of Pharmacy, Yantai University, No. 30, Qing Quan Lu, Lai Shan Qu, 264005, Yantai, Shandong Province, China

    Pengfei Yu, Qian Liu, Kun Liu & Guoying Zhang

  2. Department of Applied Biological Science, Tokyo Noko University, Saiwai-cho 3-5-8, Fuchu, Tokyo, 183-8509, Japan

    Kazumi Yagasaki

  3. Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, 58105, USA

    Erxi Wu

Authors
  1. Pengfei Yu
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  2. Qian Liu
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  3. Kun Liu
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  4. Kazumi Yagasaki
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  5. Erxi Wu
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  6. Guoying Zhang
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Corresponding author

Correspondence to Guoying Zhang.

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Pengfei Yu and Qian Liu contributed equally to this work.

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Yu, P., Liu, Q., Liu, K. et al. Matrine suppresses breast cancer cell proliferation and invasion via VEGF-Akt-NF-κB signaling. Cytotechnology 59, 219–229 (2009). https://doi.org/10.1007/s10616-009-9225-9

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