研究动态
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胃复春通过 miR-26a-5p 介导的不稳定和 MAPK 信号通路失活来靶向 KPNA2,从而抑制胃癌细胞的恶性肿瘤。

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.

发表日期:2024 Jul 09
作者: Lvli Ma, Xu Hu, Wei Zhang, Daqing Qi, Linhui Chen, Minfang Yin
来源: JOURNAL OF ETHNOPHARMACOLOGY

摘要:

胃复春(WFC)是一种常用于治疗萎缩性胃炎和肠化生的中药。迄今为止,其对胃癌(GC)的抗肿瘤作用及其潜在机制仍不清楚。我们的目的是研究WFC是否可以抑制胃癌细胞的恶性,并剖析其分子基础和相关的分子和细胞特征。胃用WFC处理癌细胞系和正常胃上皮细胞。采用CCK8实验、caspase-3活性实验、粘附实验、microRNA数据库分析、转染、RT-PCR、Western Blotting、信号通路分析、体内GC模型等检测胃癌细胞的特征变化和WFC 作用的分子机制。在这里,我们提供的数据表明,WFC 抑制 GC 的恶性细胞表型,并且这种抑制作用是通过下调致癌 KPNA2 的表达来介导的。此外,WFC 通过 miR-26a-5p 介导的基因沉默和丝裂原激活蛋白激酶 (MAPK) 的磷酸化动力学失活来下调 KPNA2。 WFC对胃癌细胞行为的抑制作用在动物模型中得到进一步证实。因此,WFC可以通过降低KPNA2的水平来发挥抑制胃癌细胞恶性的作用。此外,WFC 诱导的 miR-26a-5p 拯救和 MAPK 通路失活导致 KPNA2 表达下调。因此,我们的研究结果表明 WFC 是针对 GC 的潜在治疗选择。版权所有 © 2024。由 Elsevier B.V. 出版。
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.Copyright © 2024. Published by Elsevier B.V.