FACTORS INFLUENCING THE DRUG SENSITIZATION OF HUMAN TUMOR-CELLS FOR IN-SITU LIPOFECTION

The cisplatin induced enhancement of in situ lipofection was optimized by considering the factors that can increase the degree of sensitizat ion. Two other anticancer drugs, mechlorethamine (nitrogen mustard) an d taxol, enhanced CAT gene expression but the degree of sensitization was not as great as cisplatin. Besides human 2008 ovarian cancer cells we also found that human lung (A549) and head and neck cancer cells ( SCC 25) were transiently sensitized by cisplatin. The transfectability of the two commercially available cationic liposomes, Lipofectin and LipofectAmine, was either weak or not consistent among tumors tested. In vivo transfection efficiency of 2008 cells was the highest at 1 mu g DNA per nmol or mu g liposome with all three cationic liposomes. In vitro transfection efficiency of 2008 cells at 1:1 (mu g of DMA:nmole of DC-chol/DOPE liposome) increased in a dose-dependent manner while a t 1:10, an optimal ratio for in vitro lipofection, rapidly decreased w ith an increase in dose. This result indicated that there was a correl ation between in vivo and in vitro lipofection at 1:1 ratio for delive ring liposomal DNA. Most of the DNA injected into the tumor was concen trated in the tumor and in the skin above the tumor whether cisplatin was pre-injected or liposomes were used as carriers.