微复春通过miR-26a-5p介导的基因不稳定及MAPK信号通路的失活，抑制胃癌细胞的恶性行为

Weifuchun suppresses the malignancy of gastric cancer cells by targeting KPNA2 through miR-26a-5p-mediated destabilization and the deactivation of the MAPK signaling pathway

DOI 原文链接

用sci-hub下载

JOURNAL OF ETHNOPHARMACOLOGY

影响因子:5.4

分区:医学2区 / 全科医学与补充医学1区药学1区药物化学2区植物科学2区

发表日期:2024 Nov 15

作者: Lvli Ma, Xu Hu, Wei Zhang, Daqing Qi, Linhui Chen, Minfang Yin

DOI: 10.1016/j.jep.2024.118538

摘要

微复春（WFC）是一种常用于治疗萎缩性胃炎和肠上皮化生的中药。迄今为止，其对胃癌（GC）的抗肿瘤作用及其潜在机制尚未阐明。本研究旨在探讨WFC是否能抑制胃癌细胞的恶性行为，解析其分子基础及相关的细胞分子特征。我们用WFC处理胃癌细胞系和正常胃上皮细胞，采用CCK8法、半胱天冬酶-3活性检测、粘附检测、微RNA数据库分析、转染、RT-PCR、西方印迹、信号通路分析及体内胃癌模型，观察WFC对胃癌细胞特征的影响及其分子机制。研究结果显示，WFC能抑制胃癌细胞的恶性表型，其作用机制包括下调致瘤基因KPNA2的表达。此外，WFC通过miR-26a-5p介导的基因沉默及MAPK信号通路的去活化实现KPNA2的下调。动物模型中的验证进一步证实了WFC对胃癌细胞行为的抑制作用。因此，WFC通过降低KPNA2水平发挥抑制胃癌细胞恶性行为的作用，miR-26a-5p的激活和MAPK信号通路的去活化共同促使KPNA2表达下降。我们的研究结果提示WFC具有作为抗胃癌潜在治疗手段的潜力。

Abstract

Weifuchun (WFC) is a Traditional Chinese Medicine commonly used for treating atrophic gastritis and intestinal metaplasia. Till date, its antitumor effect on gastric cancer (GC) and the underlying mechanisms of the effect remains unelucidated.We aim to investigate if WFC can suppress the malignancy of stomach cancer cells and dissect the molecular basis and the associated molecular and cellular features.Stomach cancer cell lines and normal gastric epithelial cells were treated with WFC. CCK8 assay, caspase-3 activity assay, adhesion assay, microRNA database analysis, transfection, RT-PCR, Western Blotting, signaling pathway analysis, and in vivo GC model were employed to examine the changes in the features of the gastric cancer cells and the molecular mechanisms of the effect of WFC.Here we present data demonstrating that WFC suppresses the malignant cellular phenotypes of GC and this inhibitory effect is mediated by downregulating the expression of oncogenic KPNA2. Furthermore, WFC downregulates KPNA2 through miR-26a-5p-mediated gene silencing and the deactivated phosphorylation dynamics of mitogen-activated protein kinase (MAPK). The suppressive effect of WFC on stomach cancer cell behavior was further confirmed in animal model.Therefore, WFC can exert inhibitory effect on the malignancy of GC cells by reducing the levels of KPNA2. Moreover, the miR-26a-5p rescue and the deactivation MAPK pathway induced by WFC result in the downregulation of KPNA2 expression. Thus, our findings suggest WFC as a potential treatment option against GC.