Huaier通过抑制METTL3来调节Wnt/β-catenin信号通路,从而提高结直肠癌对奥沙利铂的敏感性。

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
ACS Applied Electronic Materials Pub Date : 2025-01-01 Epub Date: 2024-11-08 DOI:10.3892/or.2024.8840
Mingyi Huo, Zhixu Gao, Guizhen Wang, Zhiping Hou, Jining Zheng
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引用次数: 0

摘要

结直肠癌(CRC)的发病率和死亡率在中国恶性肿瘤中均居第五位。奥沙利铂(OXA)是临床治疗CRC的一线药物,但由于耐药性的产生,其抗肿瘤效果有限。本研究旨在探讨中药怀儿是否能通过影响METTL3的表达来调控Wnt/β-catenin信号通路,从而促进HCT-8/L细胞对OXA的敏感性。根据 UCSC Xena 和 Gene Expression Omnibus 数据库分析了 METTL3 的表达。构建了沉默METTL3和过表达METTL3模型,并使用细胞计数试剂盒-8和流式细胞术检测了怀尔对HCT-8/L细胞活力和凋亡的影响。采用Western印迹、逆转录定量PCR、核胞浆分离和免疫荧光等方法检测怀特对METTL3、Pgp、Wnt/β-catenin信号通路相关蛋白、凋亡相关蛋白及相关mRNA表达的影响。结果表明,METTL3表达水平高的患者总生存期较短。耐药的 CRC 细胞中 METTL3 的表达水平明显升高。通过抑制Wnt/β-catenin信号通路,沉默METTL3可促进CRC细胞凋亡并增加其对OXA的敏感性。怀尔通过抑制Wnt/β-catenin信号通路,下调了METTL3的表达,从而促进了耐药CRC细胞的凋亡,并提高了它们对OXA的敏感性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Huaier promotes sensitivity of colorectal cancer to oxaliplatin by inhibiting METTL3 to regulate the Wnt/β‑catenin signaling pathway.

Colorectal cancer (CRC) ranks fifth 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 because of the development of drug resistance. The present study aimed 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. 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 Kit‑8 and flow cytometry were used to detect the effects of Huaier on the viability and apoptosis of HCT‑8/L cells. Western blotting, reverse transcription‑quantitative 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. 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 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.

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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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