title: RNA interferences targeting the Fanconi anemia/BRCA pathway upstream genes reverse cisplatin resistance in drug-resistant lung cancer cells.
abstract: BACKGROUND
  Cisplatin is one of the most commonly used chemotherapy agent for lung cancer. The therapeutic efficacy of cisplatin is limited by the development of resistance. In this study, we test the effect of RNA interference (RNAi) targeting Fanconi anemia (FA)/BRCA pathway upstream genes on the sensitivity of cisplatin-sensitive (A549 and SK-MES-1) and -resistant (A549/DDP) lung cancer cells to cisplatin.
  
  
  RESULTS
  Using small interfering RNA (siRNA), knockdown of FANCF, FANCL, or FANCD2 inhibited function of the FA/BRCA pathway in A549, A549/DDP and SK-MES-1 cells, and potentiated sensitivity of the three cells to cisplatin. The extent of proliferation inhibition induced by cisplatin after knockdown of FANCF and/or FANCL in A549/DDP cells was significantly greater than in A549 and SK-MES-1 cells, suggesting that depletion of FANCF and/or FANCL can reverse resistance of cisplatin-resistant lung cancer cells to cisplatin. Furthermore, knockdown of FANCL resulted in higher cisplatin sensitivity and dramatically elevated apoptosis rates compared with knockdown of FANCF in A549/DDP cells, indicating that FANCL play an important role in the repair of cisplatin-induced DNA damage.
  
  
  CONCLUSIONS
  Knockdown of FANCF, FANCL, or FANCD2 by RNAi could synergize the effect of cisplatin on suppressing cell proliferation in cisplatin-resistant lung cancer cells through inhibition of FA/BRCA pathway.
authors.affiliation: Department of Radiation Oncology, Affiliated Hospital of Jiangsu University, Zhengjiang, 212001, China. daichunhua8@163.com.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Dai
authors.affiliation: Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, Zhengjiang, 212001, China. lijian541226@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, Zhengjiang, 212001, China. cp17183@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, Zhengjiang, 212001, China. jhg20050308@163.com.
authors.forename: He-Guo
authors.initials: HG
authors.lastname: Jiang
authors.affiliation: Institute of Medical Science, Jiangsu University, Zhengjiang, 212013, China. wuminxh@yeah.net.
authors.forename: Ming
authors.initials: M
authors.lastname: Wu
authors.affiliation: Institute of Medical Science, Jiangsu University, Zhengjiang, 212013, China. ycchen54@163.com.
authors.forename: Yong-Chang
authors.initials: YC
authors.lastname: Chen
mesh_terms: D019313:BRCA1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052219:Fanconi Anemia Complementation Group F Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052240:Fanconi Anemia Complementation Group L Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; C499905:FANCD2 protein, human; C499901:FANCF protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D052219:Fanconi Anemia Complementation Group F Protein; C499908:FANCL protein, human; D052240:Fanconi Anemia Complementation Group L Protein; D002945:Cisplatin