The Pharmacological Mechanism of Curcumin against Drug Resistance in Non-Small Cell Lung Cancer: Findings of Network Pharmacology and Bioinformatics Analysis

The pharmacological mechanism of curcumin against drug resistance in non-small cell lung cancer (NSCLC) remains unclear. This study aims to summarize the genes and pathways associated with curcumin action as an adjuvant therapy in NSCLC using network pharmacology, drug-likeness, pharmacokinetics, functional enrichment, protein-protein interaction (PPI) analysis, and molecular docking. Prognostic genes were identified from the curcumin-NSCLC intersection gene set for the following drug sensitivity analysis. Immunotherapy, chemotherapy, and targeted therapy sensitivity analyses were performed using external cohorts (GSE126044 and IMvigor210) and the CellMiner database. 94 curcumin-lung adenocarcinoma (LUAD) hub targets and 41 curcumin-lung squamous cell carcinoma (LUSC) hub targets were identified as prognostic genes. The anticancer effect of curcumin was observed in KEGG pathways involved with lung cancer, cancer therapy, and other cancers. Among the prognostic curcumin-NSCLC intersection genes, 20 LUAD and 8 LUSC genes were correlated with immunotherapy sensitivity in the GSE126044 NSCLC cohort; 30 LUAD and 13 LUSC genes were associated with immunotherapy sensitivity in the IMvigor210 cohort; and 12 LUAD and 13 LUSC genes were related to chemosensitivity in the CellMiner database. Moreover, 3 LUAD and 5 LUSC genes were involved in the response to targeted therapy in the CellMiner database. Curcumin regulates drug sensitivity in NSCLC by interacting with cell cycle, NF-kappa B, MAPK, Th17 cell differentiation signaling pathways, etc. Curcumin in combination with immunotherapy, chemotherapy, or targeted drugs has the potential to be effective for drug-resistant NSCLC. The findings of our study reveal the relevant key signaling pathways and targets of curcumin as an adjuvant therapy in the treatment of NSCLC, thus providing pharmacological evidence for further experimental research.