期刊
CANCER GENE THERAPY
卷 11, 期 12, 页码 830-840出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cgt.7700768
关键词
HSV thymidine kinase; tumor growth; cyclooxygenase; ganciclovir-resistant
Transduction of tumor cells with herpes simplex virus thymidine kinase (HSV-tk) gene and subsequent treatment with the prodrug ganciclovir (GCV) is the most common system utilized to date for suicide'' gene therapy of cancer. In the current report, we show that HSV-tk gene transduction enhances tumor growth rate of murine colon cancer cells, that are implanted subcutaneously in syngeneic mice, and enhances cyclooxygenase-2 (COX-2) protein expression and prostaglandin E-2 (PGE(2)) release in vitro and in vivo. It is further shown that the observed phenomenon is related to the presence of the HSV-tk sequence insert in the retroviral vector used for HSV-tk gene delivery. Transduction of murine colon cancer cells with control vector, carrying the neomycin-resistance gene alone, failed to increase tumor growth rate and COX-2 protein expression or PGE2 production. On the contrary, it even decreased tumor growth, COX-2 protein expression and PGE(2). The growth rate of HSV-tk-transduced murine tumors was significantly reduced by treatment with the selective COX-2 inhibitor nimesulide. Additionally, we demonstrate herein that both enhanced growth rate of HSV-tk-transduced murine tumors and increased levels of PGE(2) in HSV-tk-transduced cells persist upon the development of GCV resistance. Taken together, these results provide a better understanding of the direct effect of HSV-tk gene transduction on tumor cell biology and target tumor development.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据