Oxymatrine Inhibits the Proliferation and Invasion of Breast Cancer Cells via the PI3K Pathway

Abstract

Lin Guo,1 Tengfei Yang2 1Department of Gastrointestinal and Nutriology Surgery, Shengjing Hospital of China Medical University, Shenyang, LiaoNing 110004, People’s Republic of China; 2The Department of Social Service, Shengjing Hospital of China Medical University, Shenyang, LiaoNing 110004, People’s Republic of ChinaCorrespondence: Lin GuoShengjing Hospital of China Medical University, 36 Sanhao Street, Heping, Shenyang, LiaoNing 110004, People’s Republic of ChinaEmail [email protected]: Oxymatrine has been reported to possess anti-cancer activity, but its role in breast cancer (BC) is weakly defined. We investigated the anti-cancer effects of oxymatrine in human BC cells, and the underlying molecular mechanisms of these effects.Methods: BC lines were treated with oxymatrine. The MTT assay was conducted to evaluate cell viability. The cell cycle and apoptosis of BC cells were analyzed using flow cytometry and Hoechst 33258 staining. Transwell™ assays were undertaken to measure the migratory and invasive abilities of MCF-7 or MDA-MB-231 cells. Expression of phosphatidylinositol 3-kinase (PI3K), Akt, cyclin D1, cluster of differentiation (CD)K2, PARP, Gsk3β, caspase-3, matrix metalloproteinase (MMP)2 and Bax at protein and RNA levels was measured by Western blotting and quantitative real-time polymerase chain reaction.Results: Oxymatrine inhibited the proliferation of BC cells in a time-dependent manner. It induced apoptosis in a dose- and time-dependent way according to Annexin V and Hoechst 33258 staining. Oxymatrine could inhibit the invasion of BC cells as shown by the Transwell assay. Oxymatrine inhibited expression of B-cell lymphoma-2 while increasing that of Bax as well as increasing expression of caspase-3 and caspase-9. Addition of oxymatrine to BC cells attenuated the PI3K/Akt signaling pathway cascade, as evidenced by dephosphorylation of P13K and Akt.Conclusion: Oxymatrine exerts its anti-tumor effects in BC cells by abolishing the PI3K pathway. Oxymatrine may be a new compound for BC treatment.Keywords: oxymatrine, breast cancer, PI3K/Akt, proliferation, apoptosis, invasion

Keywords

• oxymatrine. breast cancer. pi3k/akt. proliferation. apoptosis. invasion.