FANCD2 depletion sensitizes cancer cells repopulation ability in vitro

Abstract

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.