[Killing effect of adenovirus vector-mediated herpes simplex virus thymidine kinase gene recombinant construct on various cancer cells].
OBJECTIVE
Adenovirus vector-mediated herpes simplex virus thymidine kinase gene (ADV-TK) transfer is one of the major gene therapy strategies for tumor. This study was designed to determine the in vitro anti-tumor efficiency of ADV-TK, a recombinant construct previously developed in our laboratory.


METHODS
Herpes simplex virus thymidine kinase (TK) gene was transduced into 14 types of cultured tumor cells with different histological origins using adenovirus vector followed by ganciclovir (GCV) medication. The killing efficiency was measured using MTT assay.


RESULTS
At the dosage of 1x10(9) viral particles/per well in the presence of 100 microg/ml GCV, ADV-TK/GCV caused effective killing of 11 out of total 14 types of tumor cells with a rate higher than 74%, the other 3 tumor cells, laryngeal epithelial cancer cells (Hep-2), hepatic cancer cells (Bel7402), and human colon cancer cells (HCT-8) were less sensitive to the ADV-TK/GCV treatment with the killing rates of 55.3%+/-2.0%, 61.3%+/-2.0%, and 63.7%+/-2.5%, respectively. Except for Hep-2, the killing efficiency caused by ADV-TK/GCV treatment was similar to that caused by cisplatin at a dosage equal to the in vivo peak concentration (5 microg/ml) in tissue.


CONCLUSIONS
ADV-TK is highly efficient for active killing of tumor cells in vitro and is promising for future clinical application.
Zhou
Jian-Feng
JF
Cancer Molecular Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Chen
Gang
G
Lu
Yun-Ping
YP
Wang
Shi-Xuan
SX
Ma
Ding
D
D000256:Adenoviridae / Q000235:genetics; D000257:Adenoviridae Infections / Q000473:pathology; D000998:Antiviral Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D015774:Ganciclovir / Q000494:pharmacology; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000494:pharmacology*; D014162:Transfection; D019076:Transgenes / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir