FANCD2 depletion sensitizes cancer cells repopulation ability in vitro.
Inactivation of Fanconi anemia/BRCA pathway in some cancers causes increased sensitivity to various drugs used for chemo-therapy. Several approaches have been suggested to artificially disrupt this pathway for better treatment. In our study, we have utilized RNA interference technique to knock-down the expression of FANCD2 and sensitize cancer cells undergoing treatment with DNA damaging agents. For this purpose, we transiently depleted FANCD2 by siRNA in a number of breast, bladder, or liver cancer cell lines and screened for mitomycin C or gamma-irradiation sensitivity changes. We could show that knocking-down FANCD2 gene expression increases sensitivity of cancer cells to mitomycin C and to less extent to gamma-rays. Importantly, this effect strongly correlates to repopulation ability of cancer cells and those cell lines with significant FANCD2 depletion revealed decreased recurrence capacity. In summary, the results we presented show proof of principle that opens new possibilities for further preclinical trials.
Lyakhovich
Alex
A
Group of Mutagenesis, Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Surralles
Jordi
J
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008297:Male; D016685:Mitomycin / Q000494:pharmacology / Q000627:therapeutic use; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy
D000903:Antibiotics, Antineoplastic; D052236:Fanconi Anemia Complementation Group D2 Protein; D034741:RNA, Small Interfering; D016685:Mitomycin