Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China; Key Laboratory of Traditional Chinese Medicine Resources and Chemistry of Hubei Province, Wuhan 430061, China.
Life Sci. 2021 Apr 1;270:119105. doi: 10.1016/j.lfs.2021.119105. Epub 2021 Jan 23.
Scopoletin is a natural anticarcinogenic and antiviral coumarin component. Many studies have proved its anti-cancer effect, and after the preliminary screening of this study, Scopoletin had the best inhibitory effect on Non-small cell lung cancer (NSCLC). But its mechanism for treating NSCLC is still unclear. Therefore, network pharmacology and molecular docking technology were used to explore the potential anti-NSCLC targets and pathways of Scopoletin. The results were verified in vitro.
First, Scopoletin was isolated from Fennel and screened to conduct cell proliferation assay on Human lung cancer cell line A549, Human colon cancer cell line HCT-116 and Human hepatoma cell line HepG2 respectively, through the MTT test. Then, the key targets and related pathways were screened through Protein-protein Interaction (PPI) network and "component-target-pathway" (C-TP) network constructed by network pharmacology. And the key targets were selected to dock with Scopoletin via molecular docking. A549 and Human normal lung epithelial cell BEAS-2B were used to verify the results, finally.
Through MTT, A549 was chosen as the test cancer cell. From network pharmacology, 16 targets, 27 signaling pathways and 16 GO items were obtained (P < 0.05). The results of PPI network and molecular docking showed that EGFR, BRAF and AKT1 were the key targets of Scopoletin against NSCLC, which were consistent with the western-blot results.
Through network pharmacology, molecular docking and experiments in vitro, Scopoletin was verified to against NSCLC through RAS-RAF-MEK-ERK pathway and PI3K/AKT pathway.
瑞香素是一种天然的抗癌和抗病毒香豆素成分。许多研究已经证明了它的抗癌作用，在本研究的初步筛选后，瑞香素对非小细胞肺癌（NSCLC）的抑制作用最好。但其治疗 NSCLC 的机制尚不清楚。因此，本研究采用网络药理学和分子对接技术，探讨瑞香素治疗 NSCLC 的潜在靶点和通路，并在体外进行验证。
首先，从茴香中分离出瑞香素，分别通过 MTT 试验对人肺癌细胞系 A549、人结肠癌细胞系 HCT-116 和人肝癌细胞系 HepG2 进行细胞增殖检测。然后，通过网络药理学构建的蛋白质-蛋白质相互作用（PPI）网络和“成分-靶-通路”（C-TP）网络筛选关键靶点及相关通路，并通过分子对接对关键靶点进行瑞香素对接。最后，在 A549 和人正常肺上皮细胞 BEAS-2B 中进行验证。
通过 MTT，选择 A549 作为测试癌细胞。从网络药理学中获得 16 个靶点、27 个信号通路和 16 个 GO 项（P<0.05）。PPI 网络和分子对接的结果表明，EGFR、BRAF 和 AKT1 是瑞香素治疗 NSCLC 的关键靶点，与 Western blot 结果一致。
通过网络药理学、分子对接和体外实验，验证了瑞香素通过 RAS-RAF-MEK-ERK 通路和 PI3K/AKT 通路抑制 NSCLC。
