|Title:||Induction of Epstein-Barr virus (EBV) reactivation in Raji cells by doxorubicin and cisplatin||Authors:||CHIH-HUNG HSU
|Issue Date:||2002||Journal Volume:||22||Journal Issue:||6 C||Start page/Pages:||4065-4071||Source:||Anticancer Research||Abstract:||
Background: Epstein-Barr virus (EBV) can be activated in B-lymphoid cells to enter the lytic cycle by various kinds of stimuli, including 12-O-tetradecanoylphorbol-1 3-acetate (TPA), butyric acid, calcium ionophore A23187, transforming growth factor-β and anti-immunoglobulin crosslinking. EBV reactivation has been clinically observed in patients receiving systemic chemotherapy. This study sought in vitro evidence to suggest whether anticancer drugs may directly contribute to the EBV reactivation. Materials and Methods: Raji cells, an EBV-containing Burkitt's lymphoma cell line, were used as the experimental model. TPA served as a positive control for chemical induction of EBV reactivation. Expression of the BZLF1 transcript of EBV and its encoded protein, ZEBRA, were examined by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and flow cytometry, respectively. Transactivation activity of ZEBRA was further assessed by a luciferase reporter assay of EBV DR-promoter activity and a flow cytometry assay assessing the endogenous expression of EA-D (BMRFl). Results: Doxorubicin and cisplatin, two commonly used anticancer agents, induced a dose-dependent up-regulation of BZLF1 mRNA and ZEBRA protein. The luciferase reporter activity and the expression of endogenous EA-D protein, also increased by doxorubicin and cisplatin, indicated an up-regulation of the transactivating activity of ZEBRA. Conclusion: These data indicate that cytotoxic anticancer drugs may up-regulate the expression and the transactivating activity of BZLF1, and suggest that systemic chemotherapy may be a risk factor for EBV reactivation in patients with EBV-associated malignancies.
|ISSN:||0250-7005||SDG/Keyword:||butyric acid; calcimycin; calcium ionophore; cisplatin; doxorubicin; immunoglobulin antibody; phorbol 13 acetate 12 myristate; transforming growth factor beta; virus protein; article; cancer cell culture; cancer chemotherapy; controlled study; dose response; drug effect; Epstein Barr virus; flow cytometry; gene expression regulation; gene function; human; human cell; in vitro study; priority journal; promoter region; protein expression; protein function; Raji cell; reporter gene; reverse transcription polymerase chain reaction; risk factor; transactivation; upregulation; virus induction; virus reactivation; Antigens, Viral; Antineoplastic Agents; B-Lymphocytes; Burkitt Lymphoma; Cisplatin; DNA-Binding Proteins; Doxorubicin; Gene Expression Regulation, Viral; Herpesvirus 4, Human; Humans; Luciferases; Reverse Transcriptase Polymerase Chain Reaction; Trans-Activators; Tumor Cells, Cultured; Up-Regulation; Viral Proteins; Virus Activation
|Appears in Collections:||腫瘤醫學研究所|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.