基于网络药理学方法和实验验证研究醋酸棉酚对胃癌细胞的抑制作用。

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.

背景：胃癌（GC）是全球主要的公共卫生问题之一，发病率和死亡率均较高。如今，传统医学可能为癌症的治疗带来希望。醋酸棉酚（GAA）是一种男性避孕药，对多种类型的癌症都有抗肿瘤作用。然而，GAA 是否会抑制 GC 的进展尚不清楚。

方法：利用 Pharmmapper 软件预测 GAA 的潜在靶点，从 GeneCard 数据库中获取 GC 相关基因。使用 Cytoscape 软件构建“GC-靶标-GAA”网络。利用 String 软件对交集基因进行 PPI 分析。使用 DAVID 软件进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析，以探讨 GAA 调节 GC 的潜在机制。采用 MTS 试验、平板克隆试验、细胞周期和凋亡试验验证 GAA 在 GC 中的作用。

结果：确定了 10 个与细胞周期进展和凋亡相关的核心基因。Cytoscape 软件可视化了许多癌症相关的信号通路。其中，PI3K-Akt 信号通路排名最高。MTS 试验和平板克隆试验表明 GAA 抑制 GC 细胞的增殖。细胞周期和凋亡试验表明 GAA 诱导 GC 细胞 G1 期细胞周期停滞和凋亡。

结论：本研究通过多个靶点和信号通路证实了 GAA 对 GC 的抗肿瘤作用。这些结果为 GAA 在临床前和临床研究中的进一步研究提供了理论依据，并表明 GAA 作为治疗 GC 的新型治疗剂具有潜在用途。