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Article

NK4 regulates 5-fluorouracil sensitivity in cholangiocarcinoma cells by modulating the intrinsic apoptosis pathway

  • Authors:
    • Xianxiu Ge
    • Youli Wang
    • Quanpeng Li
    • Hong Yu
    • Guozhong Ji
    • Lin Miao
  • View Affiliations / Copyright

    Affiliations: Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China, The Clinical Laboratory of Nanjing Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, P.R. China
  • Pages: 448-454
    |
    Published online on: April 25, 2013
       https://doi.org/10.3892/or.2013.2427
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Abstract

The aim of the present study was to investigate the role of NK4, an antagonist for hepatocyte growth factor (HGF) and the Met receptor, in regulating the response of cholangiocarcinoma (CCA) cells to 5-fluorouracil (5-FU). We established the CCA cell line, HuCC-T1, to produce abundant NK4 (Hu-NK4). Cell proliferation, cell cycle distribution, apoptosis, 5-FU metabolism and intracellular signaling were examined. There were no significant differences in the mRNA levels of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase between the mock-transfected control Hu-Em cells and Hu-NK4 cells, suggesting that NK4 expression does not alter 5-FU metabolism. Moreover, cell cycle analysis showed that 5-FU treatment caused a decrease in the proportion of cells in the G2/M phase while NK4 gene expression had little effect on the cell cycle distribution. However, 5-FU-induced apoptosis was significantly increased in the Hu-NK4 cells when compared to that in the Hu-Em cells. Further investigation revealed that NK4 gene expression enhanced 5-FU-induced caspase-3 and caspase-9 activation, and that the apoptosis of cells was associated with modulation of expression of the Bcl-2 family members. Furthermore, western blot analysis revealed that both NK4 and 5-FU were inhibitors for HGF-induced phosphorylation of Met, but they may be independent factors. Collectively, these results suggest that following 5-FU treatment in CCA cell lines, NK4 was involved in apoptosis induction through the intrinsic mitochondrial pathway. This indicates that NK4 may be an important mediator of 5-FU-induced cell death. Moreover, downregulation of NK4 in response to 5-FU may represent an intrinsic mechanism of resistance to this anticancer drug.
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Copy and paste a formatted citation
Spandidos Publications style
Ge X, Wang Y, Li Q, Yu H, Ji G and Miao L: NK4 regulates 5-fluorouracil sensitivity in cholangiocarcinoma cells by modulating the intrinsic apoptosis pathway. Oncol Rep 30: 448-454, 2013.
APA
Ge, X., Wang, Y., Li, Q., Yu, H., Ji, G., & Miao, L. (2013). NK4 regulates 5-fluorouracil sensitivity in cholangiocarcinoma cells by modulating the intrinsic apoptosis pathway. Oncology Reports, 30, 448-454. https://doi.org/10.3892/or.2013.2427
MLA
Ge, X., Wang, Y., Li, Q., Yu, H., Ji, G., Miao, L."NK4 regulates 5-fluorouracil sensitivity in cholangiocarcinoma cells by modulating the intrinsic apoptosis pathway". Oncology Reports 30.1 (2013): 448-454.
Chicago
Ge, X., Wang, Y., Li, Q., Yu, H., Ji, G., Miao, L."NK4 regulates 5-fluorouracil sensitivity in cholangiocarcinoma cells by modulating the intrinsic apoptosis pathway". Oncology Reports 30, no. 1 (2013): 448-454. https://doi.org/10.3892/or.2013.2427
Copy and paste a formatted citation
x
Spandidos Publications style
Ge X, Wang Y, Li Q, Yu H, Ji G and Miao L: NK4 regulates 5-fluorouracil sensitivity in cholangiocarcinoma cells by modulating the intrinsic apoptosis pathway. Oncol Rep 30: 448-454, 2013.
APA
Ge, X., Wang, Y., Li, Q., Yu, H., Ji, G., & Miao, L. (2013). NK4 regulates 5-fluorouracil sensitivity in cholangiocarcinoma cells by modulating the intrinsic apoptosis pathway. Oncology Reports, 30, 448-454. https://doi.org/10.3892/or.2013.2427
MLA
Ge, X., Wang, Y., Li, Q., Yu, H., Ji, G., Miao, L."NK4 regulates 5-fluorouracil sensitivity in cholangiocarcinoma cells by modulating the intrinsic apoptosis pathway". Oncology Reports 30.1 (2013): 448-454.
Chicago
Ge, X., Wang, Y., Li, Q., Yu, H., Ji, G., Miao, L."NK4 regulates 5-fluorouracil sensitivity in cholangiocarcinoma cells by modulating the intrinsic apoptosis pathway". Oncology Reports 30, no. 1 (2013): 448-454. https://doi.org/10.3892/or.2013.2427
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