Oxymatrine Suppresses Colon Cancer by reducing microRNA-21 and microRNA-141 and Targets Epithelial-Mesenchymal Transition
Department of Gastroenterology, 1Department of Endocrinology, 2Department of Interventional Radiology, The First Hospital of Hebei North University, 3College of Medicine, Hebei North University, Zhangjiakou, Hebei 075000, China
Yifeng Zhao, Department of Gastroenterology, The First Hospital of Hebei North University, 3College of Medicine, Hebei North University, Zhangjiakou, Hebei 075000, China, E-mail: firstname.lastname@example.org
Colon cancer constitutes a major challenge all over the world, which has the fourth highest incidence and the third mortality rate of all cancers. Although the therapeutic modalities have been improved in recent years, the 5 y survival rate remains low. Oxymatrine is one of the main active compounds extracted from roots of Sophora flavescens and was found with therapeutic effect for colon cancers. Recently, microRNAs have been recognized as a type of diagnostic and prognostic biomarker and are implicated in a variety of biological activities underlying the tumourogenesis and cancer development. This study firstly evaluated the anti-tumor efficacy of oxymatrine in colon cancer via cell viability assay, colony formation assay and quantification of E-cadherin/vimentin as a metric of epithelial-mesenchymal transition. MicroRNA profile was conducted to identify effective microRNAs involved in the pharmacological mechanism of oxymatrine. MicroRNA-21 and microRNA-141 were the most differentially expressed microRNAs, and overexpression of both resulted in mitigation of anti-tumor effect of oxymatrine. Phosphatase and tensin homolog was predicted to be microRNA-21 and microRNA-141, which was validated via luciferase assay. Silencing of phosphatase and tensin homolog increased the level of phosphorylated-protein kinase B and phosphorylated-nuclear factorkappa B and transfection of microRNA-21 and microRNA-141 antagomir yielded increase of them, suggesting that microRNA-21/phosphatase and tensin homolog/protein kinase B and microRNA-141/phosphatase and tensin homolog/protein kinase B were involved in the pharmacological effect of oxymatrine.