Abstract：Objective: To explore whether geniposide (GEN) can reduce gefitinib resistance in non-small cell lung cancer (NSCLC) cells by regulating the Akt/MDM2/p53 signaling pathway. Methods: Human NSCLC cell lines PC9 sensitive to gefitinib and PC9/GR resistant to gefitinib were cultured in vitro. PC9/GR cells with good growth status were stochastically assigned into Control group, L-GEN, M-GEN, H-GEN groups (5, 10, 20mg/mL GEN), and H-GEN+SC79 group (20mg/mL GEN+8μg/mL Akt activator SC79). CCK8 method was performed to detect cell proliferation. The plate cloning experiment was used to detect the ability of cells to form clones. Flow cytometry was performed to detect cell apoptosis. Transwell experiment was performed to detect cell invasion. Western blot was used to detect MDR1, MMP-2, MMP-9, and Akt/MDM2/p53 signaling pathway proteins. Results: The L-GEN group, M-GEN group, and H-GEN group had lower OD450 values of PC9/GR cells, colony formation rates, cell invasion counts, MDR1, MMP-2, MMP-9, and p-Akt/Akt, p-MDM2/MDM2 protein expression compared to the Control group, while apoptosis rates and p53 protein expression were higher (P<0.05); the H-GEN+SC79 group showed higher OD450 values, colony formation rates, cell invasion counts, MDR1, MMP-2, MMP-9, p-Akt/Akt, p-MDM2/MDM2 protein expression and lower apoptosis rates and p53 protein expression compared to the H-GEN group (P<0.05). Conclusion: GEN primarily weakens the resistance of NSCLC cells to gefitinib by inhibiting the Akt/MDM2/p53 pathway.
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2025, Vol. 31 
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