Cytotoxic effect of MTH1 gene silencing in Gemcitabine resistant breast cancer cells

Nudix hydrolase 1 (NUDT1) or human MutT homolog 1 (MTH1) catalyzes the conversion of oxidized purine nucleotides to their monophosphate forms, thus preventing their incorporation into DNA and subsequently to oxidative damage. The present study explores the relationship between MTH1 gene silencing and its outcome on the growth of gemcitabine resistant breast cancer cells named MCF7-R. For this purpose, we transfected MCF7-R cells with MTH1 specific validated siRNA. Successful transfection of siRNA and consequent cytotoxicity in MCF7-R cells was confirmed by qRT-PCR, western blotting and cell viability assay. As a result of siRNA transfection, MTH1 protein was knockdown to approximately 77% in the transfected sample and resulted in a 1.75-fold increase in sensitivity of MCF7-R cells to gemcitabine. Moreover, higher expression of p21 protein was also observed in transfected MCF7-R cells that may indicate induced cell death. This study highlights the effect of MTH1 gene silencing in drugresistant cancer cells as a mean to improve combined therapies for targeting drug-resistant cancers.