Matrine inhibits cell proliferation, invasion, and stem cell formation in hepatocellular carcinoma by regulating the ELAVL1/RBM3‐mediated Wnt/β‐catenin signaling pathway

Abstract

Matrine has been reported to exert anti‐tumor effects in various cancers, including hepatocellular carcinoma (HCC). Nevertheless, the anti‐tumor molecular mechanism of Martine in HCC is still not fully revealed. Cell proliferative ability, apoptosis, invasion, and sphere formation ability were detected using 3‐(4, 5‐dimethyl‐2‐thiazolyl)‐2, 5‐diphenyl‐2‐H‐tetrazolium bromide (MTT), 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, transwell, and sphere formation assays. CyclinD1, MMP2, RNA‐binding motif protein 3 (RBM3), embryonic lethal abnormal visual‐like protein 1 (ELAVL1), Wnt3A, and β‐catenin protein levels were assessed using western blot. RBM3 and ELAVL1 expression was measured using real‐time quantitative polymerase chain reaction (RT‐qPCR). After being predicted using Starbase, the possible interaction between ELAVL1 and RBM3 was identified using Co‐Immunoprecipitation (IP) assays. A xenograft model was used to examine how Matrine affects HCC cell growth in vivo. Matrine hindered HCC cell proliferation, invasion, and sphere formation ability, and boosted apoptosis in vitro. ELAVL1 and RBM3 content was decreased in Matrine‐treated HCC cells in a concentration‐dependent manner and was increased in HCC tissues and cell lines. Moreover, ELAVL1 might bind with RBM3 to positively regulate the stability of RBM3 mRNA. Matrine modulated the Wnt/β‐catenin signaling pathway by ELAVL1/RBM3 axis. Matrine blocked tumor growth in xenograft modes in vivo. Matrine suppressed HCC cell progression partly by regulating the ELAVL1/RBM3, providing the possible therapeutic strategy for HCC treatment.