Chang Ke, Zhu Li-Fei, Wu Ting-Ting, Zhang Si-Qi, Yu Zi-Cheng
Department of Pharmacy, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, China.
Department of Pharmacy, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China.
Chin J Integr Med. 2025 Apr;31(4):347-356. doi: 10.1007/s11655-024-4116-7. Epub 2024 Sep 27.
To explore the key target molecules and potential mechanisms of oridonin against non-small cell lung cancer (NSCLC).
The target molecules of oridonin were retrieved from SEA, STITCH, SuperPred and TargetPred databases; target genes associated with the treatment of NSCLC were retrieved from GeneCards, DisGeNET and TTD databases. Then, the overlapping target molecules between the drug and the disease were identified. The protein-protein interaction (PPI) was constructed using the STRING database according to overlapping targets, and Cytoscape was used to screen for key targets. Molecular docking verification were performed using AutoDockTools and PyMOL software. Using the DAVID database, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted. The impact of oridonin on the proliferation and apoptosis of NSCLC cells was assessed using cell counting kit-8, cell proliferation EdU image kit, and Annexin V-FITC/PI apoptosis kit respectively. Moreover, real-time quantitative PCR and Western blot were used to verify the potential mechanisms.
Fifty-six target molecules and 12 key target molecules of oridonin involved in NSCLC treatment were identified, including tumor protein 53 (TP53), Caspase-3, signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase kinase 8 (MAPK8), and mammalian target of rapamycin (mTOR). Molecular docking showed that oridonin and its key target molecules bind spontaneously. GO and KEGG enrichment analyses revealed cancer, apoptosis, phosphoinositide-3 kinase/protein kinase B (PI3K/Akt), and other signaling pathways. In vitro experiments showed that oridonin inhibited the proliferation, induced apoptosis, downregulated the expression of Bcl-2 and Akt, and upregulated the expression of Caspase-3.
Oridonin can act on multiple targets and pathways to exert its inhibitory effects on NSCLC, and its mechanism may be related to upregulating the expression of Caspase-3 and downregulating the expressions of Akt and Bcl-2.
探讨冬凌草甲素抗非小细胞肺癌（NSCLC）的关键靶分子及潜在机制。
从SEA、STITCH、SuperPred和TargetPred数据库中检索冬凌草甲素的靶分子；从GeneCards、DisGeNET和TTD数据库中检索与NSCLC治疗相关的靶基因。然后，确定药物与疾病之间的重叠靶分子。根据重叠靶点，使用STRING数据库构建蛋白质-蛋白质相互作用（PPI），并使用Cytoscape筛选关键靶点。使用AutoDockTools和PyMOL软件进行分子对接验证。使用DAVID数据库进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析。分别使用细胞计数试剂盒-8、细胞增殖EdU成像试剂盒和Annexin V-FITC/PI凋亡试剂盒评估冬凌草甲素对NSCLC细胞增殖和凋亡的影响。此外，使用实时定量PCR和蛋白质免疫印迹法验证潜在机制。
确定了56个参与NSCLC治疗的冬凌草甲素靶分子和12个关键靶分子，包括肿瘤蛋白53（TP53）、半胱天冬酶-3、信号转导子和转录激活子3（STAT3）、丝裂原活化蛋白激酶激酶8（MAPK8）和雷帕霉素靶蛋白（mTOR）。分子对接表明冬凌草甲素与其关键靶分子能自发结合。GO和KEGG富集分析揭示了癌症、凋亡、磷酸肌醇-3激酶/蛋白激酶B（PI3K/Akt）等信号通路。体外实验表明，冬凌草甲素抑制增殖、诱导凋亡、下调Bcl-2和Akt的表达，并上调Caspase-3的表达。
冬凌草甲素可作用于多个靶点和通路发挥对NSCLC的抑制作用，其机制可能与上调Caspase-3的表达以及下调Akt和Bcl-2的表达有关。
