Ganciclovir augments the lytic induction and apoptosis induced by chemotherapeutic agents in an Epstein-Barr virus-infected gastric carcinoma cell line.
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 delta 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.
Ji Jung
Eun
E
Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Mie Lee
You
Y
Lan Lee
Byung
B
Soo Chang
Mee
M
Ho Kim
Woo
W
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D002945:Cisplatin / Q000627:therapeutic use; D004357:Drug Synergism; D005472:Fluorouracil / Q000627:therapeutic use; D015774:Ganciclovir / Q000627:therapeutic use; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D066298:In Vitro Techniques; D017239:Paclitaxel / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000821:virology*
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D017239:Paclitaxel; D015774:Ganciclovir; D002945:Cisplatin; D005472:Fluorouracil