Colorectal cancer (CRC) ranks fifth in terms of incidence rate and mortality among malignant tumors in China. Oxaliplatin (OXA) is a firstâline drug for the clinical treatment of CRC, but its antitumor effect is limited because of the development of drug resistance. The present study aimed to investigate whether the traditional Chinese medicine Huaier can regulate the Wnt/βâcatenin signaling pathway by affecting the expression of METTL3, thereby promoting the sensitivity of HCTâ8/L cells to OXA. The expression of METTL3 was analyzed based on the UCSC Xena and Gene Expression Omnibus databases. Silent METTL3 and overexpression METTL3 models were constructed, and Cell Counting Kitâ8 and flow cytometry were used to detect the effects of Huaier on the viability and apoptosis of HCTâ8/L cells. Western blotting, reverse transcriptionâquantitative PCR, nuclear cytoplasmic separation and immunofluorescence were used to detect the effects of Huaier on the expression of METTL3, Pgp, Wnt/βâcatenin signaling pathwayârelated proteins, apoptosisârelated proteins and related mRNA. The results demonstrated that patients with high expression levels of METTL3 had a shorter overall survival period. The expression level of METTL3 significantly increased in drugâresistant CRC cells. Silencing METTL3 promoted apoptosis of CRC cells and increased their sensitivity to OXA by inhibiting the Wnt/βâcatenin signaling pathway. Huaier downregulated the expression of METTL3, thereby promoting apoptosis of drugâresistant CRC cells and increasing their sensitivity to OXA by inhibiting the Wnt/βâcatenin signaling pathway.
Huaier promotes sensitivity of colorectal cancer to oxaliplatin by inhibiting METTL3 to regulate the Wnt/βâcatenin signaling pathway.
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作者:Huo Mingyi, Gao Zhixu, Wang Guizhen, Hou Zhiping, Zheng Jining
期刊: | Oncology Reports | 影响因子: | 3.900 |
时间: | 2025 | 起止号: | 2025 Jan |
doi: | 10.3892/or.2024.8840 |
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