Fig. 6: BMI1 downregulation reverses FOXA1-silencing-induced cisplatin resistance in NPC cells.

CNE1 and CNE2 cell lines were transduced with plasmids containing shRNA constructs (shSCR for scrambled control, shFOXA1 for FOXA1 knockdown, and shFOXA1+shBMI1 for combined FOXA1 and BMI1 knockdown). Post-transduction, cells were exposed to cisplatin at a concentration of 0.5 μg/mL for subsequent assays. The effects of cisplatin on cell viability were assessed using the CCK8 assay (A), and the colony-formation ability was evaluated through the colony-formation assay (B). Apoptosis induction was measured by flow cytometry (C, D). Expression levels of proteins associated with drug resistance were determined by Western blotting (E). Nude mice bearing xenografts of the aforementioned cell lines were administered cisplatin at a dosage of 4 mg/kg, with treatments administered every three days for a total of three doses. Tumor growth was monitored, and representative images of the tumors (F), tumor growth curves (G), and tumor weights (H) are presented. Expression of drug resistance-related proteins in the xenograft tissues was further analyzed by immunohistochemistry (I). Scale bar = 100 μm. Data are presented as Mean ± SD with three replicates. Statistical significance was determined using one-way ANOVA followed by Tukey’s multiple comparisons test. NS, not significant; *P < 0.05, **P < 0.01 and ^#P < 0.001.