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.

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.

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.

• Authors: Chun-Hua Dai, Jian Li, Ping Chen, He-Guo Jiang, Ming Wu, Yong-Chang Chen
• Journal: Journal of biomedical science (J Biomed Sci) Vol. 22 Pg. 77 (Sep 18 2015) ISSN: 1423-0127 [Electronic] England
• PMID: 26385482 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BRCA1 Protein
• BRCA1 protein, human
• FANCD2 protein, human
• FANCF protein, human
• Fanconi Anemia Complementation Group D2 Protein
• Fanconi Anemia Complementation Group F Protein
• FANCL protein, human
• Fanconi Anemia Complementation Group L Protein
• Cisplatin

Topics

• BRCA1 Protein (antagonists & inhibitors, genetics, metabolism)
• Cell Line, Tumor
• Cisplatin (pharmacology)
• Drug Resistance, Neoplasm (drug effects, genetics)
• Fanconi Anemia Complementation Group D2 Protein (antagonists & inhibitors, genetics, metabolism)
• Fanconi Anemia Complementation Group F Protein (antagonists & inhibitors, genetics, metabolism)
• Fanconi Anemia Complementation Group L Protein (antagonists & inhibitors, genetics, metabolism)
• Humans
• Lung Neoplasms (drug therapy, genetics, metabolism, pathology)
• RNA Interference
• Signal Transduction (drug effects, genetics)