Network pharmacology‑based investigation of potential targets of Triptonodiol acting on Non-Small-Cell Lung Cancer

Abstract

Abstract Background COE is a very promising anti-tumor drug candidate extracted from the Chinese herbal, Celastrus orbiculatus Thunb, and many related studies are underway. Methods: To explore the mechanism of Triptonodiol for lung cancer treatment, we used network pharmacology and molecular docking, and ultimately protein validation. Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis were performed through David database. molecular docking was performed using PyMoL2.3.0 and AutoDock Vina software. After screening, the major targets of Triptonodiol were identified for the treatment of lung cancer. Target networks were established and PPI network topology was analyzed, Then KEGG pathway enrichment analysis was performed. Useful proteins were screened by survival analysis and Western Bolt analysis was performed. Results: Triptonodiol may regulate cell proliferation, drug resistance, MTOR, etc. by acting on GSK3B, AKT1, PIK3CA, HSP90AA1, MTOR glucose metabolism and other processes. KEGG pathway enrichment analysis showed that these targets were associated with tumor, PI3K signaling, ERBB signaling, insulin resistance, calcium signaling, etc. Molecular docking showed that the target protein GSK has good binding activity to the main active component of Triptonodiol. The results of cellular studies showed that Triptonodiol significantly reduced GSK3B levels in lung cancer cells H1299 and A549. Conclusion: The cellular level studies combined with network pharmacology and molecular docking approaches provide new ideas for the development and therapeutic application of Triptonodiol, and identified it as a potential GSK inhibitor.