Ursolic acid inhibits the growth of colorectal cancer cells through regulating the PKN2/Akt/ERK pathway by targeting SNTB1

Abstract

Background Colorectal cancer (CRC) is one of the most highly malignant tumors. Ursolic acid (UA) has been identified to exerts anti-CRC effects through the regulation of multiple genes and signaling pathways. Syntrophin beta 1 (SNTB1) has been implicated to have the potential as a new prognostic factor and therapeutic target for CRC. We wondered whether UA exert anti-CRC effects by regulating SNTB1 expression. Methods and Results CCK8 assay and colony staining was conducted to determine the cell viability and colony formation of Human CRC cell line HCT116. Lentiviral infection was employed for SNTB1 knockdown and overexpression. Western blot analysis was performed to detect the protein expression. The result shown that UA significantly inhibited cell viability and downregulated SNTB1 expression while upregulating PKN2 expression. It also decreased the ratios of p-Akt/Akt and p-ERK/ERK. UA significantly promoted the decrease of cell viability and colony formation in HCT116 cells with SNTB1 knockdown, the upregulation of PKN2 protein expression, and the downregulation of the p-Akt/Akt and p-ERK/ERK ratios. On the other hand, UA significantly inhibited the increase of cell viability and colony formation in HCT116 cells with SNTB1 overexpression, the downregulation of PKN2 protein expression, and the upregulation of the p-Akt/Akt and p-ERK/ERK ratios. Conclusion Take together, UA inhibits CRC cell growth may through regulating the PKN2/Akt/ERK pathway by targeting SNTB1. This study enriches the mechanisms underlying the anticancer effects of UA in CRC and provides new evidence for UA as a potential anti-CRC agent.