Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine

Abstract EN

Gemcitabine (2′, 2′-difluorodeoxycytidine; dFdC) is a deoxycytidine analog and is used primarily against pancreatic cancer.

The cytotoxicity of gemcitabine is due to the inhibition of DNA replication.

However, a mechanism of removal of the incorporated dFdC is largely unknown.

In this report, we discovered that nucleotide excision repair protein XPF-ERCC1 participates in the repair of gemcitabine-induced DNA damage and inactivation of XPF sensitizes cells to gemcitabine.

Further analysis identified that XPF-ERCC1 functions together with apurinic/apyrimidinic endonuclease (APE) in the repair of gemcitabine-induced DNA damage.

Our results demonstrate the importance of the evaluation of DNA repair activities in gemcitabine treatment.