Transferrin-liposome-mediated p53 sensitization of squamous cell carcinoma of the head and neck to radiation in vitro.
Wild-type (wt) p53 DNA was transfected into the radioresistant human cell line JSQ-3, established from a squamous cell carcinoma of the head and neck (SCCHN), using a transferrin-liposome system, and the ability of the introduced wt p53 to sensitize the transfected JSQ-3 cells to ionizing radiation was examined. Transferrin increased the in vitro transfection efficiency of cationic liposomes up to 70-80% in JSQ-3 cells, representing a 6- to 10-fold increase over liposome transfection alone. The exogenous wt p53 was expressed at high levels in transferrin-liposome-DNA-transfected cells and resulted in the reversion of the radioresistant phenotype of the JSQ-3 cells in a DNA dose-dependent manner. The D10 values were reduced from 6.36 +/- 0.54 Gy to 4.13 +/- 0.06 Gy, a value in the radiosensitive range. In vivo, the intratumoral injection of the transferrin-liposome system resulted in a higher number of transfected tumor cells in the JSQ-3 induced nude mouse xenografts when compared with transfection by liposome alone. The results indicate that the combination of p53 replacement gene transduction, mediated by the relatively safe transferrin-liposome system, and conventional ionizing radiation may provide a more effective treatment for head and neck cancer.
Xu
L
L
Department of Surgery, Division of Otolaryngology, Stanford University Medical Center, CA 94305-5328, USA.
Pirollo
K F
KF
Chang
E H
EH
D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000532:radiotherapy*; D004337:Drug Carriers; D016158:Genes, p53 / Q000235:genetics* / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D011836:Radiation Tolerance; D014162:Transfection / Q000235:genetics / Q000379:methods*; D014168:Transferrin / Q000008:administration & dosage; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D004337:Drug Carriers; D008081:Liposomes; D014168:Transferrin; D016159:Tumor Suppressor Protein p53