cAMP stimulates the bystander effect in suicide gene therapy of human choriocarcinoma.
In gene therapy, tumor cells expressing herpes simplex virus thymidine kinase (HSV-tk) are sensitive to ganciclovir (GCV) and HSV-tk positive cells exposed to GCV are lethal to adjacent HSV-tk negative cells. This phenomenon has been called the bystander effect, and the gap junction is thought to mediate it. In this study, sensitivity to GCV and bystander effect in a human choriocarcinoma cell line, BeWo, transfected with HSV-tk were investigated. Furthermore, the effect of 8-bromo-cAMP on bystander effect and connexin40 gene transcription were examined. HSV-tk positive cells were sensitive to GCV at the concentration of 10 micrograms/ml in a time-dependent manner. The growth of HSV-tk negative cells was inhibited when the population of cultured cells contained more than 10% HSV-tk positive cells and 8-bromo-cAMP enhanced bystander effect. 8-bromo- cAMP increased connexin40 mRNA expression and gap junctional intercellular communication.
Kunishige
I
I
Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
Samejima
Y
Y
Moriyama
A
A
Saji
F
F
Murata
Y
Y
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D002470:Cell Survival; D002822:Choriocarcinoma / Q000503:physiopathology / Q000628:therapy*; D003131:Combined Modality Therapy; D015774:Ganciclovir / Q000494:pharmacology*; D015316:Genetic Therapy; D006801:Humans; D010957:Plasmids / Q000627:therapeutic use; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D015124:8-Bromo Cyclic Adenosine Monophosphate; D013937:Thymidine Kinase; D015774:Ganciclovir