Wang Yuli, Pan Yanbin, Luo Yingbin, Wu Jianchun, Fang Zhihong, Teng Wenjing, Guan Yu, Li Yan
Clinical Medical Center of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Diagnostic Laboratory for Hematological Diseases, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Heliyon. 2023 Jul 23;9(8):e18298. doi: 10.1016/j.heliyon.2023.e18298. eCollection 2023 Aug.
Lung cancer is a malignancy characterized by high morbidity and mortality, with lung adenocarcinoma being the most prevalent subtype. Our preliminary studies have demonstrated that the Juan-Liu-San-Jie (JLSJ) prescription, a Traditional Chinese Medicine prescription, possesses anti-lung adenocarcinoma cancer properties. However, the molecular mechanism underlying the therapeutic effects of the JLSJ prescription for lung adenocarcinoma remains incompletely elucidated. To address the knowledge gap, the present study employed network pharmacology to identify potential therapeutic targets. Specifically, the study utilized TCMSP, TCMID, and related references, as well as ChemMapper, to identify and predict the main active components and potential targets. Additionally, differentially expressed genes associated with the disease were obtained from the microarray dataset GSE19804 and GSE118370. The protein-protein Interaction network and Target-pathway network were then constructed. We also conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and subsequently presented the top 20 enriched pathways. The results indicated that the anti-lung cancer effects of JLSJ prescription may be attributed to its ability to mediate apoptosis of tumor cells, potentially through the PI3K/Akt signaling pathway. Then, a series of in vitro and in vivo experiments were conducted to validate the molecular mechanism predicted by network pharmacology. The findings of the in vivo study suggested that the JLSJ prescription could inhibit the growth of xenograft tumors of lung adenocarcinoma with fewer adverse effects. Also, the in vitro experiments corroborated that the JLSJ prescription could induce apoptosis of A549 cells. Furthermore, the upregulation of pro-apoptosis-related proteins and mRNAs, coupled with the downregulation of anti-apoptotic-related proteins and mRNAs, was observed. In conclusion, inducing apoptosis by inhibiting the PI3K/Akt signaling pathway was one of the underlying mechanisms by which the JLSJ prescription exerted its anti-lung adenocarcinoma effect.
肺癌是一种发病率和死亡率都很高的恶性肿瘤，其中肺腺癌是最常见的亚型。我们的初步研究表明，中药方剂“软坚散结方”具有抗肺腺癌的特性。然而，“软坚散结方”治疗肺腺癌的分子机制仍未完全阐明。为了填补这一知识空白，本研究采用网络药理学来确定潜在的治疗靶点。具体而言，该研究利用中药系统药理学数据库与分析平台（TCMSP）、中药整合数据库（TCMID）及相关参考文献，以及化学映射器（ChemMapper）来识别和预测主要活性成分及潜在靶点。此外，从基因芯片数据集GSE19804和GSE118370中获取与该疾病相关的差异表达基因。随后构建了蛋白质-蛋白质相互作用网络和靶标-通路网络。我们还进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析，并列出了前20条富集通路。结果表明，“软坚散结方”的抗肺癌作用可能归因于其介导肿瘤细胞凋亡的能力，可能是通过PI3K/Akt信号通路。然后进行了一系列体外和体内实验，以验证网络药理学预测的分子机制。体内研究结果表明，“软坚散结方”可以抑制肺腺癌异种移植瘤的生长，且副作用较少。此外，体外实验证实，“软坚散结方”可以诱导A549细胞凋亡。此外，还观察到促凋亡相关蛋白和mRNA上调，同时抗凋亡相关蛋白和mRNA下调。总之，通过抑制PI3K/Akt信号通路诱导凋亡是“软坚散结方”发挥抗肺腺癌作用的潜在机制之一。
