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

Ponsilp Zeekpudsa13, Veerapol Kukongviriyapan13, Laddawan Senggunprai13, Banchob Sripa23 and Auemduan Prawan13*

Author Affiliations

1 Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand

2 Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

3 Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, Thailand

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Journal of Experimental & Clinical Cancer Research 2014, 33:11  doi:10.1186/1756-9966-33-11

Published: 24 January 2014



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.


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.


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.


These results suggest that inhibition of NQO1 could enhance the susceptibility of CCA to an array of chemotherapeutic agents.

NAD(P)H-quinone oxidoreductase 1 (NQO1); Cholangiocarcinoma (CCA); 5-fluorouracil (5-FU); Doxorubicin (Doxo); Gemcitabine (Gem); p53