Tan Boyu, Lan Xiaoxu, Zhang Yifan, Liu Pai, Jin Qiyao, Wang Zhiqiang, Liang Zhidong, Song Wei, Xuan Ye, Sun Yunxiao, Li Youjie
Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
Department of Pediatrics, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China.
Exp Ther Med. 2024 Mar 28;27(6):239. doi: 10.3892/etm.2024.12527. eCollection 2024 Jun.
The present study aimed to investigate the effect and mechanism of Pulsatilla compounds on lung adenocarcinoma. The representative drug chosen was the compound 23-HBA. GeneCards, Swiss target prediction, DisGeNET and TCMSP were used to screen out related genes, and MTT and flow cytometry assays were used to verify the inhibitory effect of Pulsatilla compounds on the proliferation of lung adenocarcinoma cells. Subsequently, the optimal target, peroxisome proliferator-activated receptor (PPAR)-γ, was selected using bioinformatics analysis, and its properties of low expression in lung adenocarcinoma cells and its role as a tumor suppressor gene were verified by western blot assay. The pathways related to immunity and inflammation, vascular function, cell proliferation, differentiation, development and apoptosis with the highest degree of enrichment and the mechanisms were explored through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Finally, the clinical prognosis in terms of the survival rate of patients in whom the drug is acting on the target was analyzed using the GEPIA database. The results indicated that Pulsatilla compounds can inhibit the proliferation of lung adenocarcinoma cells by blocking the cell cycle at the G phase. Subsequently, the related PPAR-γ gene was verified as a tumor suppressor gene. Further analysis demonstrated that this finding was related to the PPAR signaling pathway and mitochondrial reactive oxygen species (ROS) production. Finally, the clinical prognosis was found to be improved, as the survival rate of patients was increased. In conclusion, Pulsatilla compounds were indicated to inhibit the viability and proliferation of lung adenocarcinoma H1299 cells, and the mechanism of action was related to PPAR-γ, the PPAR signaling pathway and mitochondrial ROS. The present study provides novel insight to further explore the treatment of lung adenocarcinoma.
本研究旨在探讨白头翁化合物对肺腺癌的作用及机制。选用的代表性药物为化合物23 - HBA。利用GeneCards、瑞士靶点预测、DisGeNET和中药系统药理学数据库与分析平台（TCMSP）筛选相关基因，并采用MTT法和流式细胞术检测白头翁化合物对肺腺癌细胞增殖的抑制作用。随后，通过生物信息学分析选择最佳靶点过氧化物酶体增殖物激活受体（PPAR）-γ，并通过蛋白质免疫印迹法验证其在肺腺癌细胞中低表达的特性及其作为肿瘤抑制基因的作用。通过基因本体论（Gene Ontology）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes）分析，探索与免疫和炎症、血管功能、细胞增殖、分化、发育和凋亡相关的富集程度最高的通路及其机制。最后，使用GEPIA数据库分析该药物作用于靶点的患者生存率方面的临床预后。结果表明，白头翁化合物可通过将细胞周期阻滞在G期来抑制肺腺癌细胞的增殖。随后，相关的PPAR -γ基因被验证为肿瘤抑制基因。进一步分析表明，这一发现与PPAR信号通路和线粒体活性氧（ROS）产生有关。最后，发现临床预后得到改善，因为患者的生存率提高了。总之，白头翁化合物被证明可抑制肺腺癌H1299细胞的活力和增殖，其作用机制与PPAR -γ、PPAR信号通路和线粒体ROS有关。本研究为进一步探索肺腺癌的治疗提供了新的见解。
