Ganciclovir augments the lytic induction and apoptosis... : Anti-Cancer Drugs (original) (raw)
PRECLINICAL REPORTS
Ganciclovir augments the lytic induction and apoptosis induced by chemotherapeutic agents in an Epstein–Barr virus-infected gastric carcinoma cell line
Ji Jung, Euna; Mie Lee, Youa c; Lan Lee, Byunga; Soo Chang, Meeb; Ho Kim, Wooa b
aCancer Research Institute
bDepartment of Pathology, Seoul National University College of Medicine, Seoul
cDepartment of Natural Sciences, School of Life Sciences and Biotechnology, Kyungpook National University, Daegu, South Korea
Correspondence to W.H. Kim, Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Seoul 110-799, South Korea.
Tel: +82 2 740 8269; fax: +82 2 765 5600;
e-mail: [email protected]
Sponsorship: This work was supported by grant no. A050229 of Good Health R&D Project, Ministry of Health & Welfare, R. O. K.
Received 2 May 2006 Revised form accepted 30 August 2006
The first two authors contributed equally to this work.
Abstract
Epstein–Barr virus is an oncogenic herpesvirus and has been associated with several human malignancies, including gastric cancer. In Epstein–Barr virus-associated gastric cancer, Epstein–Barr virus is found in virtually all tumor cells, but rarely in normal epithelial cells, thus implying that Epstein–Barr virus-targeting therapies are likely to be an effective treatment strategy. Using the SNU-719 gastric cancer cell line, which is naturally infected with Epstein–Barr virus, we found that the chemotherapeutic agents, such as 5-fluorouracil, _cis_-platinum and taxol, induced the expressions of BMRF1, BZLF1 and BRLF1 proteins that are usually found in the lytic form of the virus. This effect was found to require various signal transduction pathways involving phosphatidylinositol 3′ kinase, mitogen-activated protein/extracellular signal-regulated kinase, protein kinase C δ and p38 mitogen-activated protein kinase. Moreover, the combination of ganciclovir with these agents increased the lytic transformation and induced apoptosis in Epstein–Barr virus-associated gastric carcinoma. We conclude that ganciclovir enhances the therapeutic efficacy of 5-fluorouracil, _cis_-platinum and taxol in Epstein–Barr virus-positive gastric cancer cells. It is hoped that this information will be found useful during the establishment of treatment strategies for Epstein–Barr virus-associated gastric cancer.
© 2007 Lippincott Williams & Wilkins, Inc.