Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Sanguisorba officinalis L. (SOL), a traditional Chinese herbal medicine called Diyu, has been shown to have potent antitumor effects. However, the role of SOL in suppressing NSCLC remains unknown.Methods: Network pharmacology was employed for acquiring the potential targets and mechanisms of SOL in NSCLC. Based on the predictions of network pharmacology, we used CCK8 and EdU assays to investigate cell proliferation, flow cytometry to investigate apoptosis, wound healing assay to investigate cell migration, and transwell assay to investigate cell invasion in vitro. Western blot was employed for detecting the potential proteins, including signaling pathways and apoptosis. The A549-bearing athymic nude mice were employed to verify the effect on cell proliferation and apoptosis in vivo.Results: SOL significantly inhibited the proliferation, migration and invasion of NSCLC cells in a dose-dependent manner. Flow cytometry showed that the apoptotic ratio and ROS level of NSCLC cells increased significantly with increasing concentrations. AKT and the PI3K-AKT signaling pathway were analyzed as the most relevant target and pathway via network pharmacology predictions. Western blotting revealed that the expression levels of p-PI3K, p-AKT, and p-mTOR in NSCLC cells treated with SOL were significantly downregulated, while cleaved PARP-1 and caspase-3 were upregulated in a dose-dependent manner. The results in the mouse xenograft model were consistent with those in NSCLC cell lines.Conclusion: SOL downregulated the PI3K/AKT/mTOR signaling pathway to suppress NSCLC.

中文翻译：

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基于网络药理学和实验研究的地榆通过下调 PI3K/AKT/mTOR 信号通路抑制非小细胞肺癌

背景：非小细胞肺癌（NSCLC）是最常见的肺癌类型。地榆大号.(SOL) 是一种名为地榆的传统中草药，已被证明具有强大的抗肿瘤作用。然而，SOL在抑制NSCLC中的作用仍然未知。方法：采用网络药理学研究SOL在NSCLC中的潜在靶点和作用机制。基于网络药理学的预测，我们使用CCK8和EdU测定法研究细胞增殖，流式细胞术研究细胞凋亡，伤口愈合测定法研究细胞迁移，transwell测定法研究细胞侵袭体外. Western blot用于检测潜在的蛋白质，包括信号通路和细胞凋亡。采用A549荷瘤裸鼠验证对细胞增殖和凋亡的影响体内结果：SOL呈剂量依赖性显着抑制NSCLC细胞的增殖、迁移和侵袭。流式细胞术显示NSCLC细胞的凋亡率和ROS水平随着浓度的增加而显着增加。AKT 和 PI3K-AKT 信号通路被分析为最相关的靶标和通路通过网络药理学预测。蛋白质印迹显示，用 SOL 处理的 NSCLC 细胞中 p-PI3K、p-AKT 和 p-mTOR 的表达水平显着下调，而裂解的 PARP-1 和 caspase-3 以剂量依赖的方式上调。在小鼠异种移植模型中的结果与在NSCLC细胞系中的结果一致。结论：SOL通过下调PI3K/AKT/mTOR信号通路抑制NSCLC。