背景:胃复春(WFC)是一种常用于治疗萎缩性胃炎和肠上皮化生的中药。直到日期,其对胃癌(GC)的抗肿瘤作用及其潜在机制仍未阐明。
目的: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。
方法:用WFC处理胃癌细胞株和正常胃上皮细胞。CCK8测定,caspase-3活性测定,粘附试验,microRNA数据库分析,转染,RT-PCR,西方印迹,信号通路分析,和体内GC模型用于检查胃癌细胞特征的变化以及WFC作用的分子机制。
结果:在这里,我们提供的数据表明WFC抑制了GC的恶性细胞表型,并且这种抑制作用是通过下调致癌KPNA2的表达而介导的。此外,WFC通过miR-26a-5p介导的基因沉默和丝裂原活化蛋白激酶(MAPK)的失活磷酸化动力学下调KPNA2。在动物模型中进一步证实了WFC对胃癌细胞行为的抑制作用。
结论:因此,WFC可通过降低KPNA2水平对GC细胞的恶性程度产生抑制作用。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是一种潜在的抗GC治疗方案.
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.