Induction of chemosensitivity in nasopharyngeal carcinoma cells using a human papillomavirus regulatory sequence and the thymidine kinase gene.
Nasopharyngeal carcinoma (NPC) is a human cancer of epithelial cell origin. Infection by Epstein-Barr virus has been shown to be closely associated with this tumor. Recent studies have indicated that another common epitheliotropic virus, human papillomavirus (HPV), is also found in a significant number of NPC cases. In this study, we evaluated the feasibility of using the HPV regulatory long control region (LCR) to drive the expression of the thymidine kinase (tk) gene to achieve chemosensitivity for gene therapeutic treatment of NPC. Testing HPV-11-LCR-tk constructs in NPC cell lines in the presence of ganciclovir (GCV) led to 50-60% cell death of transfected cells. The therapeutic efficacy was further tested in an in vivo model using nude mice transplanted with tumors derived from transfected NPC cells. Injection of 50 mg/kg body weight GCV twice daily for 14 days resulted in visually complete regression of the transplanted NPC tumor loads within 20 days after GCV treatment. Taken together, results from this pilot study indicate the feasibility of the development of a gene therapeutic protocol based on the chemosensitive gene constructs described in this paper.
Chow
Kai-Ping N
KP
Department of Microbiology and Immunology, Medical College, Chang Gung University, Taoyuan, Taiwan, ROC.
Lu
Hsi-Chi
HC
Chou
Huar-Fen
HF
Liu
Hao-Ping
HP
Hsieh
Shie-Liang
SL
Chang
Yu-Sun
YS
Choo
Kong-Bung
KB
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D006224:Cricetinae; D004279:DNA, Viral / Q000235:genetics; D005240:Feasibility Studies; D015774:Ganciclovir / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics*; D011355:Prodrugs / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D012045:Regulatory Sequences, Nucleic Acid; D013937:Thymidine Kinase / Q000008:administration & dosage* / Q000235:genetics* / Q000494:pharmacology; D014162:Transfection; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D004279:DNA, Viral; D011355:Prodrugs; D013937:Thymidine Kinase; D015774:Ganciclovir