Document Detail

Transfection of oral cancer cells mediated by transferrin-associated lipoplexes: mechanisms of cell death induced by herpes simplex virus thymidine kinase/ganciclovir therapy.
MedLine Citation:
PMID:  17049485     Owner:  NLM     Status:  MEDLINE    
The Herpes Simplex Virus thymidine kinase (HSV-tk) suicide gene/ganciclovir (GCV) approach has been used for the treatment of a variety of cancers. The purpose of the present study was to evaluate the cytotoxic effect of ganciclovir in oral squamous cancer cells, previously transfected with HSV-tk gene delivered by transferrin-associated complexes (Tf-lipoplexes), as well as to investigate the mechanisms involved in the bystander effect and in the process of cell death. The delivery of HSV-tk gene to the oral cancer cells, HSC-3 and SCC-7, mediated by Tf-lipoplexes followed by ganciclovir treatment resulted in essentially 100% cytotoxicity, the observed toxic effect being dependent both on GCV dose and incubation time. Cell death was shown to occur mainly by an apoptotic process. Different experimental approaches demonstrated that the observed cytotoxicity was mainly due to diffusion of the toxic agent into neighbouring, non-transfected cells, via gap junctions. Preliminary in vivo studies in a murine model for oral squamous cell carcinoma have shown a significant inhibition of tumor growth upon injection of Tf-lipoplexes carrying HSV-tk followed by intraperitonal injection of GCV, as compared to controls.
Sílvia S Neves; Ana B Sarmento-Ribeiro; Sérgio P Simões; Maria C Pedroso de Lima
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-09-14
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1758     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-11-07     Completed Date:  2007-01-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1703-12     Citation Subset:  IM    
Center for Neuroscience and Cell Biology, Coimbra, Portugal.
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MeSH Terms
Antibiotics, Antineoplastic / therapeutic use
Carcinoma, Squamous Cell / drug therapy*,  pathology
Cell Death / drug effects
Dose-Response Relationship, Drug
Ganciclovir / therapeutic use*
Gene Therapy / methods
Liposomes / chemistry,  metabolism*
Mouth Neoplasms / drug therapy*,  pathology
Simplexvirus / enzymology*
Thymidine Kinase / genetics*,  metabolism
Time Factors
Transfection / methods
Transferrin / chemistry,  metabolism*
Tumor Cells, Cultured
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Liposomes; 11096-37-0/Transferrin; 82410-32-0/Ganciclovir; EC Kinase

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