Huaier promotes sensitivity of colorectal cancer to oxaliplatin by inhibiting METTL3 to regulate the Wnt/β-catenin signaling pathway

Abstract Objective Colorectal cancer (CRC) ranks in the top five in terms of incidence rate and mortality among malignant tumors in China. Oxaliplatin (OXA) is a first-line drug for the clinical treatment of CRC, but its antitumor effect is limited due to the development of drug resistance. The aim of this study was to investigate whether the traditional Chinese medicine Huaier can regulate the Wnt/β-catenin signaling pathway by affecting the expression of METTL3, thereby promoting the sensitivity of HCT-8/L cells to OXA. Methods We analyzed the expression of METTL3 based on the UCSC Xena database and Gene Expression Omnibus (GEO) database. We constructed silent METTL3 and overexpression METTL3 models, and used CCK-8 and flow cytometry to detect the effects of Huaier on the viability and apoptosis of HCT-8/L cells. Western blot, qRT-PCR, nuclear cytoplasmic separation, and immunofluorescence were used to detect the effects of Huaier on the expression of METTL3, Pgp, Wnt/β-catenin signaling pathway–related proteins, apoptosis-related proteins, and related mRNA. Results Patients with high expression levels of METTL3 had a shorter overall survival period. The expression level of METTL3 significantly increased in drug-resistant CRC cells. Silencing METTL3 promoted apoptosis of CRC cells and increased their sensitivity to OXA by inhibiting the Wnt/β-catenin signaling pathway. Huaier downregulated the expression of METTL3, thereby promoting apoptosis of drug-resistant CRC cells and increasing their sensitivity to OXA by inhibiting the Wnt/β-catenin signaling pathway.