Differential Functions of C- and N-Terminal Hepatitis B x Protein in Liver Cells Treated with Doxorubicin in Normoxic or Hypoxic Condition

Autor: Billy C.S. Leung, Davor Kin-Fan Chau, George G. Chen, Sukying Chun, Haitao Zhang, Paul B.S. Lai
Rok vydání: 2012
Předmět:
Proteomics
Anatomy and Physiology
Non-Clinical Medicine
viruses
Cell Culture Techniques
Cancer Treatment
lcsh:Medicine
Apoptosis
p38 Mitogen-Activated Protein Kinases
Biochemistry
Molecular Cell Biology
Viral Regulatory and Accessory Proteins
Hypoxia
lcsh:Science
Cells
Cultured
Multidisciplinary
Liver Diseases
Liver cell
Liver Neoplasms
Gene Expression Regulation
Neoplastic
HBx
Liver
Oncology
Medicine
Research Article
medicine.drug
Gene Expression Regulation
Viral
Cell Survival
Gastroenterology and Hepatology
Biology
Protein Chemistry
Cell Line
Tumor
In Situ Nick-End Labeling
medicine
Humans
MTT assay
Doxorubicin
Viability assay
Protein Interactions
Cell growth
lcsh:R
Proteins
Chemotherapy and Drug Treatment
Hypoxia-Inducible Factor 1
alpha Subunit
Molecular biology
digestive system diseases
Protein Structure
Tertiary
Cell culture
Mutation
Trans-Activators
Cancer research
lcsh:Q
Zdroj: PLoS ONE, Vol 7, Iss 11, p e50118 (2012)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0050118
Popis: Hepatitis viral B x protein (HBx), a hepatocarcinogen, is frequently mutated. Hypoxia influences the growth of HCC and also the sensitivity of tumor cells to treatments. We aimed to test the role of HBx and acute hypoxia in the efficacy of chemotherapy. In this study, we established 4 Chang liver cell lines with the full-length HBx (HBx), the first 50 amino acids of N-terminal HBx (HBx/50), the last 104 amino acids of C-terminal HBx (HBx/51) and empty vector (CL), respectively. MTT and TNUEL assays were used to assess cell viability and apoptosis respectively. Western blot was used to determine the expression of relevant proteins. Results showed that among 4 cell lines, doxorubicin was most effective in decreasing the viability and enhancing apoptosis in HBx/51 cells, while HBx/50 cells were most resistant to the treatment. Cells in hypoxia were more susceptible to doxorubicin than cells in normoxia. Hypoxia facilitated the Bid cleavage especially in HBx/51 cells via phosphorylating p38 MAPK. p38 MAPK inhibitor significantly reduced the tBid level and increased cell viability. In conclusion, N-terminal HBx and C-terminal HBx function differentially in their ability to regulate cell growth, with the former being promotive but the latter being inhibitory. The acute hypoxia may overcome the HBx-induced resistance and facilitate the chemotherapy.
Databáze: OpenAIRE
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