Potentials and limitations of adenovirus-p53 gene therapy for brain tumors.
10.3346/jkms.2000.15.3.315
- Author:
Yong Kil HONG
1
;
Young Ae JOE
;
Youn Joo YANG
;
Kwan Sung LEE
;
Byung Chul SON
;
Shin Soo JEUN
;
Dong Sup CHUNG
;
Kyung Keun CHO
;
Chun Kun PARK
;
Moon Chan KIM
;
Hoon Kyo KIM
;
W K Alfred YUNG
;
Joon Ki KANG
Author Information
1. Department of Neurosurgery, The Catholic University of Korea, Seoul. hongyk@cmc.cuk.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Genes, p53;
Gene Therapy;
Glioma;
Brain Neoplasms;
Adenoviridae
- MeSH:
Adenoviruses, Human;
Animal;
Brain Neoplasms/therapy*;
Cell Division;
Gene Therapy*;
Genetic Vectors;
Glioma/therapy*;
Human;
Mice;
Mice, Nude;
Protein p53/physiology;
Protein p53/genetics*;
Rats;
Tumor Cells, Cultured
- From:Journal of Korean Medical Science
2000;15(3):315-322
- CountryRepublic of Korea
- Language:English
-
Abstract:
We investigated the antineoplastic potentials of recombinant adenovirus containing wild-type p53 cDNA (Ad5CMV-p53) for malignant gliomas. In four human glioma cell lines (U-251 and LG expressing endogenous mutant p53, and U-87 and EFC-2 expressing wild-type p53) and two rat glioma cell lines (9L and C6, each expressing mutant and wild-type p53), gene transfer efficiency determined by X-gal staining and Western blotting was varied (10-99% at 10-500 multiplicity of infection, MOI). Growth inhibitory effect was drastic (>90% at 100 MOI) in U-251 cells and only moderate or minimal in other cell lines harboring wild-type p53 or low gene transfer efficiency. Ex vivo transduction of U-251 cells with Ad5CMV-p53 suppressed the in vivo tumorigenicity of the cells. Histopathologic examination for Ad5CMV-p53 toxicity to rat brains showed inflammatory reactions in half of the tested brains at 10(8) MOI. U-251 cells were inoculated intracerebrally in nude mice and injected Ad5CMV-p53 into the tumor, in which neither the tumor suppression nor the survival benefit was observed. In conclusion, heterogeneity of the cellular subpopulations of malignant glioma in p53 status, variable and insufficient gene delivery to tumor, and adenoviral toxicity to brain at higher doses may be limiting factors to be solved in developing adenovirus-p53 gene therapy for malignant gliomas.
