2. Academic Validation
  3. Hepatitis C Virus-Induced FUT8 Causes 5-FU Drug Resistance in Human Hepatoma Huh7.5.1 Cells

Hepatitis C Virus-Induced FUT8 Causes 5-FU Drug Resistance in Human Hepatoma Huh7.5.1 Cells

  • Viruses. 2019 Apr 24;11(4):378. doi: 10.3390/v11040378.
Shu Li 1,  Xiao-Yu Liu 2,  Qiu Pan 3,  Jian Wu 4,  Zhi-Hao Liu 5,  Yong Wang 6,  Min Liu 7,  Xiao-Lian Zhang 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology and Medical Research Institute, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China. [email protected].
  • 2 State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology and Medical Research Institute, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China. [email protected].
  • 3 State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology and Medical Research Institute, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China. [email protected].
  • 4 State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology and Medical Research Institute, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China. [email protected].
  • 5 State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology and Medical Research Institute, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China. [email protected].
  • 6 State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology and Medical Research Institute, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China. [email protected].
  • 7 State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology and Medical Research Institute, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China. [email protected].
  • 8 State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology and Medical Research Institute, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China. [email protected].
PMID: 31022917 DOI: 10.3390/v11040378
Abstract

Hepatitis C virus (HCV) is a major cause of human chronic liver disease and hepatocellular carcinoma. Our recent studies showed that α1,6-fucosyltransferase (FUT8), a key glycosyltransferase, was the most up-regulated glycosyltransferase after the HCV Infection of human hepatocellular carcinoma Huh7.5.1 cells. Here, we further studied the effects and possible mechanism of FUT8 on the proliferation of HCV and chemotherapy-resistance of HCV-infected Huh7.5.1 cells. The effects of FUT8 on the proliferation and drug resistance of HCV-infected Huh7.5.1 cells were analyzed by flow cytometry analysis (FCM), quantitative real-time polymerase chain reaction (qRT-PCR), Western blot analysis and Lactate Dehydrogenase (LDH) release assay. Results: We found that FUT8 not only promoted Huh7.5.1 proliferation by activating PI3K-AKT-NF-κB signaling, but also stimulated the expression of the drug-resistant proteins P-glycoprotein (P-gp) and multidrug resistance related protein 1 (MRP1) and enhanced the 5-fluorouracil (5-FU) chemo-resistance of Huh7.5.1 cells. Silencing of FUT8 reduced the cell proliferation and increased the 5-FU sensitivity of HCV-infected Huh7.5.1 cells. Inhibition of P-gp and MRP1 increased the 5-FU drug sensitivity in HCV infected Huh7.5.1 cells. HCV-induced FUT8 promotes proliferation and 5-FU resistance of Huh7.5.1 cells. FUT8 may serve as a therapeutic target to reverse chemotherapy resistance in HCV-infected Huh7.5.1 cells.

Keywords

5-fluorouracil (5-FU); drug-resistance; hepatitis C virus (HCV); α-1,6 fucosyltransferase (FUT8).

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