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 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.
Hsiao
M
M
Department of Neurosurgery, Stanford University Medical Center, California 94305, USA.
Tse
V
V
Carmel
J
J
Tsai
Y
Y
Felgner
P L
PL
Haas
M
M
Silverberg
G D
GD
D000818:Animals; D001932:Brain Neoplasms / Q000628:therapy*; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D008055:Lipids; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; D051381:Rats; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use
D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; D016159:Tumor Suppressor Protein p53; C087276:(3-dimyristyloxypropyl)(dimethyl)(hydroxyethyl)ammonium; C020888:1,2-dielaidoylphosphatidylethanolamine