Abstract: Objective To investigate the effect of silencing Bmi-1 expression in reversing cisplatin resistance in human lung
cancer cells and explore the possible mechanisms. Methods Cisplatin-resistant A549/DDP cells with small interference RNA
(siRNA)-mediated Bmi-1 expression silencing were examined for cisplatin sensitivity using MTT assay and alterations in cell
cycle distribution and apoptosis with flow cytometry, and the changes in cell senescence was assessed using β-galactosidase
staining. The protein expressions of Bmi-1, P14ARF, P16INK4a, P53, P21, Rb and ubi-H2AK119 in the cells were determined with
Western blotting. Results A549/DDP cells showed significantly higher Bmi-1 expression than A549 cells. After
siRNA-mediated Bmi-1 silencing, A549/DDP cells showed significantly enhanced cisplatin sensitivity with an increased IC50
from 40.3±4.1 μmol/L to 18.3±2.8 μmol/L (P<0.01) and increased cell percentage in G0/G1 phase from (48.9±2.3)% to (78.7±7.6)%
(P<0.01). Silencing Bmi-1 did not cause significant changes in the cell apoptosis rate but induced obvious senescence
phenotype in A549/DDP cells with down-regulated expression of ubi-H2AK119 and up-regulated expressions of P14ARF,
P16INK4a, P53，P21 and Rb. Conclusion Silencing Bmi-1 by RNA interference can induce cell senescence and resensitize A549/
DDP cells to cisplatin possibly by regulating INK4a/ARF/Rb senescence pathway.