Background: Cisplatin resistance remains a significant challenge in the treatment of lung cancer, severely limiting its therapeutic efficacy. Solanine has shown potential in sensitizing resistant cancer cells to chemotherapy. The Beclin1-YAP1 signaling axis plays a pivotal role in autophagy regulation and drug resistance. Based on this pathway, the present study aimed to investigate the molecular mechanisms through which solanine overcomes cisplatin resistance in lung cancer.

Methods: A549/cisplatin (DDP) cells were divided into four groups: control, DDP, solanine, and DDP + solanine. Cell invasion and proliferation were evaluated using Transwell assays, scratch wound healing assays, and colony formation assays. The expression levels of Beclin1, Yes-associated protein 1 (YAP1), P-glycoprotein (P-gp), lung resistance-related protein (LRP), transcriptional coactivator with PDZ-binding motif (TAZ), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and mammalian target of rapamycin (mTOR) were analyzed by Western blotting. Additionally, Beclin1 overexpression was employed to validate the impact of solanine.

Results: The DDP, solanine, and DDP + solanine groups demonstrated a significant reduction in the number of invading cells and colonies, as well as a marked decrease in cell migration distance compared to the control group (p < 0.05). Additionally, the expression of proteins associated with DDP resistance was significantly downregulated. The DDP + solanine group showed a substantial decrease in colony formation, invasion, and cell migration distance compared to either the DDP or solanine groups alone. Additionally, overexpression of Beclin1 was found to attenuate the reversal effect of solanine.

Conclusion: Solanine enhances cisplatin sensitivity in A549/DDP cells in vitro, potentially through modulation of the Beclin1-YAP1 signaling pathway.