Li Hong, Lin Jing, Yang Fei, Deng Junzhu, Lai Jia, Zeng Jing, Zou Wenjun, Jiang Nan, Huang Qianqian, Li Hua, Liu Jian, Li Mao, Zhong Zhirong, Wu Jianming
School of Pharmacy, Southwest Medical University, Luzhou, China.
Laboratory of Ethnopharmacology, Tissue-orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China.
Front Pharmacol. 2022 Nov 24;13:1054803. doi: 10.3389/fphar.2022.1054803. eCollection 2022.
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. 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. 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 . 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 . 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 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. SOL downregulated the PI3K/AKT/mTOR signaling pathway to suppress NSCLC.
非小细胞肺癌（NSCLC）是最常见的肺癌类型。中药地榆（L（SOL））已被证明具有强大的抗肿瘤作用。然而，地榆在抑制NSCLC中的作用尚不清楚。采用网络药理学方法来获取地榆在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检测法研究细胞增殖，流式细胞术检测细胞凋亡，伤口愈合检测法研究细胞迁移，Transwell检测法研究细胞侵袭。采用蛋白质免疫印迹法检测潜在蛋白，包括信号通路和凋亡相关蛋白。使用荷A549细胞的裸鼠来验证对细胞增殖和凋亡的影响。地榆以剂量依赖性方式显著抑制NSCLC细胞的增殖、迁移和侵袭。流式细胞术显示，随着浓度增加，NSCLC细胞的凋亡率和活性氧水平显著升高。作为网络药理学预测中最相关的靶点和通路，对AKT和PI3K-AKT信号通路进行了分析。蛋白质免疫印迹法显示，用地榆处理的NSCLC细胞中p-PI3K、p-AKT和p-mTOR的表达水平显著下调，而裂解的PARP-1和caspase-3以剂量依赖性方式上调。小鼠异种移植模型中的结果与NSCLC细胞系中的结果一致。地榆通过下调PI3K/AKT/mTOR信号通路来抑制NSCLC。
