Oxymatrine Inhibits Malignant Behaviors of Breast Cancer Cells by Inhibiting miR-188 Expression to Up-Regulate Phosphatase and Tensin Homolog (PTEN)

Abstract

Oxymatrine has been applied to anti-cancer therapies for various cancers. The present study aimed to investigate the potential impact of miR-188 on breast cancer (BC) cell progression and underlying mechanism. After establishment of a rat model of BC, rats were administered with oxymatrine (4 mg/kg, 8 mg/kg), Xihuang pill (XH) (positive control), and miR-188 mimic (1 mg/kg) followed by analysis of tumor growth, the expression of miR-188, MMP-9, MMP-2, and PTEN, and BC cell behaviors. Oxymatrine significantly decreased tumor incidence and reduced tumor mass (p<0.05) with 8 mg/kg intervention group and positive control group exhibiting higher tumor inhibition rate (p<0.05). In addition, oxymatrine or XH effectively reduced cell proliferation, invasion and migration rate. Of note, compared to 4 mg/kg oxymatrine, 8 mg/kg oxymatrine and XH showed more significantly inhibitory effects on BC cells. Moreover, oxymatrine or XH significantly downregulated miR-188, MMP-9, and MMP-2 and upregulated PTEN. Mechanically, PTEN was indicated as the target of miR-188 with specific binding between them. In conclusion, Oxymatrine inhibits BC cell behaviors through down-regulation of miR-188 to increase PTEN expression. This study might provide a new basis for the management of BC.