Oncology Department, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100071, People's Republic of China.
Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China.
Drug Des Devel Ther. 2022 Feb 17;16:375-395. doi: 10.2147/DDDT.S343149. eCollection 2022.
Yin-Huo-Tang (YHT) is a classic traditional Chinese prescription, used to prevent lung adenocarcinoma (LUAD) relapse by "nourishing yin and clearing heat". In this study, the mechanism of YHT in LUAD recurrence was investigated.
Firstly, the bioactive compounds and targets of YHT, as well as related targets of LUAD recurrence, were collected from public databases. The protein-protein interaction network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to find the pivotal compounds, hub genes, functional annotation and main pathways. Subsequently, RNA sequencing of recurrent tumor tissues from Lewis lung carcinoma mice treated with YHT was used to explore the main pathways. At the same time, pathways screened by network pharmacology and RNA sequencing analysis were considered the most important pathways. Finally, liquid chromatography mass spectrometry was used to validate the pivotal active ingredients. Molecular docking technology was performed to validate the binding association between the hub genes and the pivotal active ingredients. PCR and WB analysis were used to validate the main pathways.
There were 128 active compounds and 419 targets interacting with YHT and LUAD recurrence. Network analysis identified 4 pivotal compounds, 28 hub genes and 30 main pathways. Sphingolipid signaling pathway was the common main pathway in network pharmacology and RNA sequencing results. The hub gene related to the sphingolipid signaling pathway was S1PR5. Qualitative phytochemical analysis confirmed the presence of 3 pivotal compounds, namely stigmasterol, nootkatone and ergotamine. The molecular docking verified that the pivotal compounds could good affinity with S1PR5. The PCR and WB analysis verified YHT suppressed Lewis lung cancer cells proliferation and migration by inhibiting the sphingolipid signaling pathway.
The potential mechanism and therapeutic effect of YHT against the recurrence of LUAD may be ascribed to inhibition of the sphingolipid signaling pathway.
银花活肺汤（YHT）是一种经典的中药方剂，用于“滋阴清热”预防肺腺癌（LUAD）复发。本研究探讨了 YHT 在 LUAD 复发中的作用机制。
首先，从公共数据库中收集 YHT 的生物活性化合物和靶点，以及 LUAD 复发的相关靶点。进行蛋白质-蛋白质相互作用网络、基因本体论和京都基因与基因组百科全书富集分析，以找到关键化合物、枢纽基因、功能注释和主要途径。随后，使用 YHT 治疗的 Lewis 肺癌小鼠复发性肿瘤组织的 RNA 测序来探讨主要途径。同时，网络药理学和 RNA 测序分析筛选的途径被认为是最重要的途径。最后，使用液相色谱-质谱联用技术验证关键活性成分。分子对接技术验证枢纽基因与关键活性成分的结合关系。PCR 和 WB 分析验证主要途径。
YHT 与 LUAD 复发相互作用有 128 种活性化合物和 419 个靶点。网络分析确定了 4 种关键化合物、28 个枢纽基因和 30 条主要途径。鞘脂信号通路是网络药理学和 RNA 测序结果的共同主要途径。与鞘脂信号通路相关的枢纽基因是 S1PR5。定性植物化学分析证实了 3 种关键化合物的存在，即豆甾醇、诺卡酮和麦角胺。分子对接验证了关键化合物与 S1PR5 具有良好的亲和力。PCR 和 WB 分析验证了 YHT 通过抑制鞘脂信号通路抑制 Lewis 肺癌细胞的增殖和迁移。
YHT 抑制 LUAD 复发的潜在机制和治疗效果可能归因于抑制鞘脂信号通路。
