Killing effect of the herpes simplex virus thymidine kinase/ganciclovir enzyme/prodrug system on human nasopharyngeal carcinoma cells.
A promising new approach for the gene therapy of cancer is the introduction of the herpes simplex virus thymidine kinase (HSV tk) gene into tumour cells, where the HSV tk gene product converts the nontoxic prodrug ganciclovir (GCV) into its cytotoxic metabolite. We constructed a recombinant plasmid containing the HSV tk gene using standard molecular biology techniques in order to investigate whether the HSV tk/GCV enzyme/prodrug system could kill the human nasopharyngeal carcinoma cell line HNE-1. The recombinant plasmid pcDNA3.1(-) CMV. TK was transfected into the HNE-1 cells by electroporation. The expression of HSV tk by the transfected HNE-1/TK cells was confirmed by mRNA amplification and Western blotting. The growth of HNE-1/TK cells was inhibited by GCV in a dose-dependent manner. The HSV tk/GCV system also demonstrated a considerable bystander effect on co-cultured wild type HNE-1 cells. We conclude that the HSV tk/GCV system could be used as gene therapy for nasopharyngeal carcinoma.
Tang
Y
Y
ENT Department, Xiangya Hospital, Central South University, Changsha, Hunan Province, China. shiw888@yahoo.com.cn
Li
J
J
Zhao
S
S
Liu
J
J
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D024201:Bystander Effect; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018274:Electroporation; D015774:Ganciclovir / Q000494:pharmacology*; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011355:Prodrugs / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D000970:Antineoplastic Agents; D011355:Prodrugs; D012333:RNA, Messenger; D013937:Thymidine Kinase; D015774:Ganciclovir