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Hepatitis C Virus-Induced FUT8 Causes 5-FU Drug Resistance in Human Hepatoma Huh7.5.1 Cells
- Source :
- Viruses, Volume 11, Issue 4, Viruses, Vol 11, Iss 4, p 378 (2019)
- Publication Year :
- 2019
-
Abstract
- Hepatitis C virus (HCV) is a major cause of human chronic liver disease and hepatocellular carcinoma. Our recent studies showed that &alpha<br />1,6-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-&kappa<br />B 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.
- Subjects :
- 0301 basic medicine
Antimetabolites, Antineoplastic
Carcinoma, Hepatocellular
Hepatitis C virus
lcsh:QR1-502
Drug resistance
Hepacivirus
medicine.disease_cause
lcsh:Microbiology
Article
Flow cytometry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
drug-resistance
Western blot
Virology
Lactate dehydrogenase
Cell Line, Tumor
medicine
Gene silencing
Humans
Gene Silencing
Cell Proliferation
medicine.diagnostic_test
5-fluorouracil (5-FU)
Cell growth
Chemistry
Liver Neoplasms
virus diseases
medicine.disease
Fucosyltransferases
α-1,6 fucosyltransferase (FUT8)
digestive system diseases
030104 developmental biology
Infectious Diseases
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Cancer research
Fluorouracil
hepatitis C virus (HCV)
Signal Transduction
Subjects
Details
- ISSN :
- 19994915
- Volume :
- 11
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Viruses
- Accession number :
- edsair.doi.dedup.....3396ac2c4566887bcd591fb430185d24