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RNA interferences targeting the Fanconi anemia/BRCA pathway upstream genes reverse cisplatin resistance in drug-resistant lung cancer cells.
- Source :
-
Journal of biomedical science [J Biomed Sci] 2015 Sep 18; Vol. 22, pp. 77. Date of Electronic Publication: 2015 Sep 18. - Publication Year :
- 2015
-
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.<br />Result: 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.<br />Conclusion: 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.
- Subjects :
- Cell Line, Tumor
Humans
BRCA1 Protein antagonists & inhibitors
BRCA1 Protein genetics
BRCA1 Protein metabolism
Cisplatin pharmacology
Drug Resistance, Neoplasm drug effects
Drug Resistance, Neoplasm genetics
Fanconi Anemia Complementation Group D2 Protein antagonists & inhibitors
Fanconi Anemia Complementation Group D2 Protein genetics
Fanconi Anemia Complementation Group D2 Protein metabolism
Fanconi Anemia Complementation Group F Protein antagonists & inhibitors
Fanconi Anemia Complementation Group F Protein genetics
Fanconi Anemia Complementation Group F Protein metabolism
Fanconi Anemia Complementation Group L Protein antagonists & inhibitors
Fanconi Anemia Complementation Group L Protein genetics
Fanconi Anemia Complementation Group L Protein metabolism
Lung Neoplasms drug therapy
Lung Neoplasms genetics
Lung Neoplasms metabolism
Lung Neoplasms pathology
RNA Interference
Signal Transduction drug effects
Signal Transduction genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1423-0127
- Volume :
- 22
- Database :
- MEDLINE
- Journal :
- Journal of biomedical science
- Publication Type :
- Academic Journal
- Accession number :
- 26385482
- Full Text :
- https://doi.org/10.1186/s12929-015-0185-4