氧化苦参碱通过抑制PKM2糖酵解增强膀胱癌顺铂敏感性机制研究

Abstract

Bladder cancer (BCa) is a malignancy in the genitourinary tract. Aerobic glycolysis is involved in the progression and chemoresistance of BCa. Oxymatrine is an alkaloid from the root of Sophora flavescens Ait. and possesses anticancer properties. This study aimed to validate whether oxymatrine can inhibit BCa progression by regulating glycolysis. The effects of oxymatrine on BCa cellsin vitro were evaluated using CCK-8 assays, colony formation assays, wound healing assays, and transwell assays. To determine the levels of lactate production and glucose consumption, a lactate assay kit and a glucose assay kit were used. Pyruvate kinase M2 (PKM2) and glucose transporter type 1 (GLUT1) expression levels were measured using immunoblotting, immunofluorescent staining, and immunohistochemistry analysis. A mouse model of BCa was constructed to explore the impact of oxymatrine (40 mg/kg) combined with cisplatin (5 mg/kg) on BCa in vivo. Oxymatrine suppressed BCa cell viability, proliferation, migration, and invasion. Oxymatrine attenuated glycolysis and downregulated the expression of PKM2 and GLUT1 in BCa cells. Overexpression of PKM2 reversed the suppressive effects of oxymatrine on the malignant phenotypes of BCa cells, while silencing PKM2 further enhanced them. Moreover, oxymatrine (40 mg/kg) or cisplatin (5 mg/kg) restrained BCa tumor growth and PKM2 expression in vivo, and these effects were further enhanced by the combination treatment with oxymatrine and cisplatin. Overall, oxymatrine inhibits cell growth and enhances cisplatin sensitivity in BCa by attenuating PKM2-mediated glycolysis, suggesting that oxymatrine is a potential anti-BCa agent.