INTRACAVITARY LIPOSOME-MEDIATED P53 GENE-TRANSFER INTO GLIOBLASTOMA WITH ENDOGENOUS WILD-TYPE P53 IN-VIVO RESULTS IN TUMOR SUPPRESSION AND LONG-TERM SURVIVAL

A cavitary glioblastoma model was created by injection of RT-2 cells, which express endogenous wild type p53, into the peritoneal cavity of nude mice. This model developed multiple layers of tumor cells invadin g the peritoneal surface and was used to mimic the postoperative surgi cal cavity remaining after glioblastoma (GEM) excision in patients. Rh odamine labeled DMRIE/DOPE + DNA complexes were found to penetrate at least 20 tumor cell layers. Injection of p53 gene/liposome complexes i nto the intraperitoneal cavity after the tumor was established resulte d in massive tumor necrosis. Prominent staining of human p53 protein u sing the DO-1 antibody was found in tumor cells near the necrotic lesi ons. Tumor explants expressed human p53 protein and showed a 54 % grow th reduction in an in vitro growth assay, Further, DMRIE/DOPE mediated p53 gene transfection significantly increased the mean survival time of tumor bearing mice compared to vector control. These results demons trate the efficiency of using exogenous wild type p53 to suppress glio blastoma cell with endogenous wild type p53 in vivo through liposome m ediated transfection method. (C) 1997 Academic Press.