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 c ell line JSQ-3, established from a squamous cell carcinoma of the head and neck (SCCHN), using a transferrin-liposome system, and the abilit y of the introduced wt p53 to sensitize the transfected JSQ-3 cells to ionizing radiation was examined, Transferrin increased the in vitro t ransfection efficiency of cationic liposomes up to 70-80% in JSQ-3 cel ls, representing a 6- to 10-fold increase over liposome transfection a lone, The exogenous wt p53 was expressed at high levels in transferrin -liposome-DNA-transfected cells and resulted in the reversion of the r adioresistant phenotype of the JSQ-3 cells in a DNA dose-dependent man ner, The D-10 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 numb er of transfected tumor cells in the JSQ-3 induced nude mouse xenograf ts when compared with transfection by liposome alone. The results indi cate that the combination of p53 replacement gene transduction, mediat ed by the relatively safe transferrin-liposome system, and conventiona l ionizing radiation may provide a more effective treatment for head a nd neck cancer.