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Cytotechnology

, Volume 59, Issue 3, pp 219–229 | Cite as

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

  • Pengfei Yu
  • Qian Liu
  • Kun Liu
  • Kazumi Yagasaki
  • Erxi Wu
  • Guoying Zhang
JAACT Special Issue

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.

Keywords

Matrine Anticancer agents Human breast cancer Proliferation Invasion MMP-9/MMP-2 Akt signaling Nuclear factor κ

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

Notes

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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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Pengfei Yu
    • 1
  • Qian Liu
    • 1
  • Kun Liu
    • 1
  • Kazumi Yagasaki
    • 2
  • Erxi Wu
    • 3
  • Guoying Zhang
    • 1
  1. 1.Laboratory of Molecular Pharmacology, School of PharmacyYantai UniversityYantaiChina
  2. 2.Department of Applied Biological ScienceTokyo Noko UniversityFuchuJapan
  3. 3.Department of Pharmaceutical SciencesNorth Dakota State UniversityFargoUSA

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