Promotion of Qiyu Sanlong Decoction on the sensitivity of subcutaneous tumor model of lung cancer to cisplatin by promoting ferroptosis via CBS/GPX4
Objective:To investigate the potential mechanism of Qiyu Sanlong Decoction in the enhancement of cisplatin sensitivity in lung cancer based on Bioinformatics and animal experiments.Methods:TCGA database was analyzed to obtain differential genes for lung cancer and cisplatin resistance.The artificial intelligence strategy was used to predict the targets of Qiyu Sanlong Decoction.The intersection was constructed and the core targets were screened for GO and KEGG enrichment analysis.Gene Dependence analysis and Molecular docking was performed for core target,and finally A549/DDP cells were used to construct the subcutaneous tumor model of lung cancer for validation.Results:Qiyu Sanlong Decoction had 186 potential effective targets associated with cisplatin resistance in lung cancer.The main biological processes included cellular response to hydrogen peroxide,and cellular oxidant detoxification,and the main functional pathways included glutathione metabolism,and platinum drug resistance.Genetic dependency analysis identified CBS as a core target associated with ferroptosis.Molecular docking showed that CBS had good affinity for the core active ingredients of Qiyu Sanlong Decoction,with the best binding affinity for peimisine.The animal experiments results showed that Qiyu Sanlong Decoction combined with cisplatin could result in large sheets of necrotic cells in the tumor tissues.Compared with the cisplatin group,the combination group was able to up-regulate the expression of 4HNE and TFR proteins,and down-regulate the expression of CBS and GPX4 proteins compared with the cisplatin group.Conclusion:Qiyu Sanlong Decoction was able to increase the sensitivity of cisplatin-resistant tumor tissues to cisplatin,and its mechanism may be through inhibiting ferroptosis-related proteins CBS and GPX4 to play a role.
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