Background: Gastric cancer (GC) is one of the major public health problems worldwide with high morbidity and mortality. Nowadays, traditional medicine may hold promise for the treatment of cancers. Gossypol-acetic acid (GAA) is a male contraceptive agent that shows anti-tumor effects on multiple types of cancers. However, whether GAA would inhibit the progression of GC remained unclear.
Methods: The potential targets of GAA were predicted by the Pharmmapper software and GC-related genes were obtained from the GeneCard database. The “GC-targets-GAA” network was constructed using the Cytoscape software. The PPI analysis of intersection genes was performed using the String software. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the DAVID software to explore the potential mechanism underlying the regulatory role of GAA in GC. The MTS test, plate cloning test, cell cycle and apoptosis assays were used to verify the function of GAA in GC.
Results: Ten hub genes related to cell cycle progression and apoptosis were identified. Many cancer-related signaling pathways were visualized by the Cytoscape software. Among them, the PI3K-Akt signaling pathway was the highest-ranked pathway. The MTS test and plate cloning test showed that GAA inhibited the proliferation of GC cells. The cell cycle and apoptosis assays showed that GAA induced G1 phase cell cycle arrest and apoptosis in GC cells.
Conclusion: Our study demonstrated the anti-tumor effect of GAA on GC through multiple targets and signaling pathways. These results provided a theoretical basis for further investigation of GAA in preclinical and clinical studies, and suggested the potential use of GAA as a novel therapeutic agent for the treatment of GC.



中文翻译：

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基于网络药理学方法和实验验证的棉酚乙酸对胃癌细胞抑制作用的研究

背景：胃癌（GC）是全球主要的公共卫生问题之一，发病率和死亡率都很高。如今，传统医学有望治疗癌症。棉酚乙酸 (GAA) 是一种男性避孕药，对多种癌症具有抗肿瘤作用。然而，GAA是否会抑制GC的进展仍不清楚。
方法：通过Pharmmapper软件预测GAA的潜在靶点，并从GeneCard数据库中获得GC相关基因。“GC-targets-GAA”网络是使用 Cytoscape 软件构建的。使用String软件进行交叉基因的PPI分析。使用 DAVID 软件进行基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 通路分析，以探索 GAA 在 GC 中的调节作用的潜在机制。MTS试验、平板克隆试验、细胞周期和细胞凋亡试验用于验证GAA在GC中的功能。
结果：鉴定了十个与细胞周期进程和细胞凋亡相关的中枢基因。Cytoscape 软件可视化了许多与癌症相关的信号通路。其中，PI3K-Akt信号通路是排名最高的通路。MTS试验和平板克隆试验表明GAA抑制GC细胞的增殖。细胞周期和细胞凋亡测定显示GAA诱导GC细胞的G1期细胞周期停滞和细胞凋亡。
结论：我们的研究通过多个靶点和信号通路证明了 GAA 对 GC 的抗肿瘤作用。这些结果为进一步研究GAA在临床前和临床研究中提供了理论基础，并提出了GAA作为治疗GC的新型治疗剂的潜在用途。