Suppression of NAD(P)H-quinone oxidoreductase 1 enhanced the susceptibility of cholangiocarcinoma cells to chemotherapeutic agents

Background: cholangiocarcinoma (cca) is highly resistant to most of the known chemotherapeutic treatments. nad(p)h-quinone oxidoreductase 1 (nqo1) is an antioxidant/detoxifying enzyme recently recognized as an important contributor to chemoresistance in some human cancers. however,the contribution of nqo1 to chemotherapy resistance in cca is unknown. methods. two cca cell lines,kku-100 and kku-m214,with high and low nqo1 expression levels,respectively,were used to evaluate the sensitivity to chemotherapeutic agents; 5-fluorouracil (5-fu),doxorubicin (doxo),and gemcitabine (gem). nqo1 and/or p53 expression in kku-100 cells were knocked down by sirna. nqo1 was over-expressed in kku-m214 cells by transfection with pcmv6-xl5-nqo1 expression vector. cca cells with modulated nqo1 and/or p53 expression were treated with chemotherapeutic agents,and the cytotoxicity was assessed by srb assay. the mechanism of enhanced chemosensitivity was evaluated by western blot analysis. results: when nqo1 was knocked down,kku-100 cells became more susceptible to all chemotherapeutic agents. conversely,with over-expression of nqo1 made kku-m214 cells more resistant to chemotherapeutic agents. western blot analysis suggested that enhanced chemosensitivity was probably due to the activation of p53-mediated cell death. enhanced susceptibility to chemotherapeutic agents by nqo1 silencing was abolished by knockdown of p53. conclusions: these results suggest that inhibition of nqo1 could enhance the susceptibility of cca to an array of chemotherapeutic agents. © 2014 zeekpudsa et al.; licensee biomed central ltd.