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 invading the peritoneal surface and was used to mimic the postoperative surgical cavity remaining after
glioblastoma (GBM) excision in patients.
Rhodamine labeled
DMRIE/DOPE +
DNA complexes were found to penetrate at least 20
tumor cell layers. Injection of p53 gene/
liposome complexes into the intraperitoneal cavity after the
tumor was established resulted in massive
tumor necrosis. Prominent staining of human p53
protein using the DO-1 antibody was found in
tumor cells near the necrotic lesions.
Tumor explants expressed human p53
protein and showed a 54% growth 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 demonstrate the efficiency of using exogenous wild type p53 to suppress
glioblastoma cell with endogenous wild type p53 in vivo through
liposome mediated transfection method.