期刊
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
卷 33, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/1756-9966-33-11
关键词
NAD(P)H-quinone oxidoreductase 1 (NQO1); Cholangiocarcinoma (CCA); 5-fluorouracil (5-FU); Doxorubicin (Doxo); Gemcitabine (Gem); p53
类别
资金
- Thailand Research Fund [RMU5380027]
- National Research University Project and the Office of Higher Education Commission through SHeP-GMS of Khon Kaen University
- Liver Fluke and Cholangiocarcinoma Research Center
- Faculty of Medicine, Khon Kaen University [I 56108]
- Office of the Higher Education Commission
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.
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