title: [Effect of silencing Bmi-1 expression in reversing cisplatin resistance in lung cancer cells and its mechanism].
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, P14(ARF), P16(INK4a), 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 P14(ARF), P16(INK4a), P53, P21 and Rb.
  
  
  CONCLUSIONS
  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.
authors: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. E-mail: maonan123@126.com.
authors: Nan
authors: N
authors: Mao
authors: Guansheng
authors: G
authors: He
authors: Jinjun
authors: J
authors: Rao
authors: Lin
authors: L
authors: Lv
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D063150:Polycomb Repressive Complex 1 / Q000235:genetics*; D034741:RNA, Small Interfering
chemical_list: D000970:Antineoplastic Agents; C069077:BMI1 protein, human; D034741:RNA, Small Interfering; D063150:Polycomb Repressive Complex 1; D002945:Cisplatin