4 years ago

Matrine reversed multidrug resistance of breast cancer MCF-7/ADR cells through PI3K/AKT signal pathway

Huan-min Gao, Chang-Sheng Wei, Zhi Zhang, Song Zhang, Bing-Gang Zhou
Matrine is an alkaloid extracted from a Chinese herb Sophora flavescens Ait, and has been used clinically for breast cancer with marked therapeutic efficacy in China. However, the mechanism has not been well known. Thus the present study was to explore if Matrine reverse multidrug resistance for breast cancer cells though regulating PI3K/AKT signal pathway. Methyl thiazolyl tetrazolium (MTT) assay was used to detect the inhibitory action; Annexin V to detect apoptosis; Fluorospectrophotometry to examine intracellular adriamycin (ADR) accumulation and Western-blot to label the proteins of P-glycoprotein(P-gp), MRP1, PTEN, p-AKT, Bcl-2, Bax and Caspase-3. Matrine (0-2.5) mg/mL inhibited MCF-7/ADR cell growth and induced apoptosis (P<0.01). 0.2mg/mL Matrine could increase the intracellular concentration of ADR, the accumulation in MCF-7 /ADR cells increased 3.56 times. Compared with control group, 0.6, 1.2 mg/mL Matrine reduced protein expressions of P-gp, MRP1, p-AKT, Bcl-2, but increased PTEN, Bax and Cleaved Caspase-3 gradually and unchanged caspase-3. Matrine was more likely to reduce the expression of P-gp, MRP1 and p-AKT at the same inhibition radio of Matrine (0.6 mg/mL) and MK2206 (0.05 umol/L). Matrine inhibited MCF-7/ADR cell growth, induced apoptosis and reversed multidrug resistance for breast cancer cells through regulating the downstream apoptosis factors of PI3K/AKT signal pathway by decreasing cell phosphorylation of AKT level. This article is protected by copyright. All rights reserved

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jcb.26502

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