Investigating therapeutic potential of Evodiamine by identifying differentially expressed genes in cisplatin resistance non-small cell lung cancer.

Cisplatin resistance poses a significant barrier to effective chemotherapy in non-small cell lung cancer, often driven by epithelial-mesenchymal transition regulators such as ZEB2. In this study, we explored the therapeutic potential of Evodiamine (Evo), a natural alkaloid derived from Evodia rutaecarpa, to overcome cisplatin resistance in A549 lung cancer cells. Using MTT assay, we evaluated the cytotoxic effects of Evo on both A549 parental and A549 cisplatin-resistant(A549CR) cells (IC-50 4 µM & 2 µM respectively), observing a dose-dependent reduction in cell viability. Quantitative real-time PCR analysis revealed that Evo treatment significantly downregulated ZEB2 expression along with key drug-resistance genes, suggesting its role in reversing the resistant phenotype. In silico molecular docking and network analysis further supported strong binding interactions between Evo and ZEB2, TGM2, MMP1, CD24, PDK4, highlighting its potential as a direct inhibitor. By further evaluating anti-proliferative, anti-migratory property with apoptotic inducing potential of Evo, we found there is a significant effect on A549 and A549CR cells. Together, these findings demonstrate that ZEB-2 can be an effective target of Evo mediating cisplatin resistance pathways and sensitize resistant lung cancer cells to cisplatin, providing a promising combinatorial therapeutic strategy to enhance NSCLC treatment efficacy.