Shao Xiang, Liu Yuping, Jiang Cuihua, Sun Yue, Zhang Qiyang, Gu Jialin, Huo Jiege, Hu Canhong
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, China.
Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, China.
Evid Based Complement Alternat Med. 2022 May 2;2022:2662288. doi: 10.1155/2022/2662288. eCollection 2022.
With a high incidence and limited treatments, gastric cancer (GC) seriously threatens human health worldwide. Weikang Keli (WK) is a compound prescription summed up from clinical experience. In our previous studies, WK has been proved to exert antitumor effects. However, there are no research studies to discuss and verify its mechanism as a compound.
The aim of the study is to explore the potential molecular mechanism of WK in the treatment of GC with the aid of network pharmacology and verify it through experiments.
Related databases were used to obtain genes and targets of WK and gastric cancer. A protein-protein interaction (PPI) network is constructed and visualized by Cytoscape 3.7.2. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to analyze core targets. The cell viability of MFC and BGC-823 cells was determined by CCK8. Immunofluorescence was used to determine autophagy of GC cells. Moreover, the effect of WK on the MAPK signaling pathway in GC cells and tumor tissues of ICR mice was detected by Western blot.
A total of 106 cross targets of WK and GC were obtained. According to the enrichment analysis of GO and KEGG, we target the MAPK signaling pathway to discuss the mechanism of WK on GC. Cell experiments proved that WK inhibited the viability of gastric cancer cells in a dose-dependent and time-dependent manner. Autophagosome aggregation and an increase in the expression of an autophagy marker protein LC3-II can also be observed in WK groups. Further animal experiments showed that the tumor inhibition rate of WK showed a dose-effect relationship. Moreover, the expressions of p-JNK, p-p38, and p-ERR1/2 proteins in the MAPK signaling pathway in WK Group were downregulated both in the cell and animal experiments, compared with the blank control group.
WK showed an explicit antitumor effect on gastric cancer through the MAPK signaling pathway, and the curative effect varies in different concentrations. Besides, in model mice, the antitumor effect of high-dose WK group is close to that of platinum. This study provided a theoretical basis for the application of WK in the clinical treatment of gastric cancer.
胃癌（GC）发病率高且治疗手段有限，严重威胁全球人类健康。胃康颗粒（WK）是根据临床经验总结出的复方制剂。在我们之前的研究中，已证明WK具有抗肿瘤作用。然而，尚无研究探讨和验证其作为复方制剂的作用机制。
本研究旨在借助网络药理学探索WK治疗GC的潜在分子机制，并通过实验进行验证。
利用相关数据库获取WK和胃癌的基因及靶点。通过Cytoscape 3.7.2构建并可视化蛋白质-蛋白质相互作用（PPI）网络。采用基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析来分析核心靶点。用CCK8法测定MFC和BGC-823细胞的细胞活力。采用免疫荧光法测定GC细胞的自噬情况。此外，通过蛋白质印迹法检测WK对ICR小鼠GC细胞和肿瘤组织中MAPK信号通路的影响。
共获得106个WK与GC的交叉靶点。根据GO和KEGG的富集分析，我们针对MAPK信号通路探讨WK对GC的作用机制。细胞实验证明，WK以剂量和时间依赖性方式抑制胃癌细胞活力。在WK组中还可观察到自噬体聚集以及自噬标记蛋白LC3-II表达增加。进一步的动物实验表明，WK的抑瘤率呈剂量效应关系。此外，与空白对照组相比，在细胞和动物实验中，WK组MAPK信号通路中p-JNK、p-p38和p-ERR1/2蛋白的表达均下调。
WK通过MAPK信号通路对胃癌显示出明确的抗肿瘤作用，且疗效因浓度不同而有所差异。此外，在模型小鼠中，高剂量WK组的抗肿瘤效果接近铂类药物。本研究为WK在胃癌临床治疗中的应用提供了理论依据。
