Antitumor Activity of TRAIL Recombinant Adenovirus in Human Malignant Glioma Cells.
10.3346/jkms.2005.20.6.1046
- Author:
Ki Uk KIM
1
;
Su Yeong SEO
;
Ki Young HEO
;
Young Hyun YOO
;
Hye Jin KIM
;
Hyeong Sik LEE
;
Sun Seob CHOI
;
Tae Ho HWANG
;
Hye Jeong LEE
Author Information
1. Brain Tumor Research, Dong-A University College of Medicine, Busan, Korea. hjlee@dau.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Glioma;
TRAIL receptor 3;
Adenoviral Vector;
Gene Therapy;
Mice, SCID
- MeSH:
Adenoviridae/*genetics;
Animals;
Apoptosis;
Apoptosis Regulatory Proteins/*genetics;
Cell Line, Tumor;
Gene Expression;
Gene Therapy/*methods;
Glioma/pathology/*therapy;
Humans;
Membrane Glycoproteins/*genetics;
Mice;
Mice, SCID;
Neoplasm Transplantation;
Research Support, Non-U.S. Gov't;
Transplantation, Heterologous;
Tumor Necrosis Factor-alpha/*genetics
- From:Journal of Korean Medical Science
2005;20(6):1046-1052
- CountryRepublic of Korea
- Language:English
-
Abstract:
Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL) has been reported to specifically kill malignant cells but to be relatively nontoxic to normal cells. One of disadvantages to previous in vivo protocols was the need for large quantities of TRAIL recombinant protein to suppress tumor growth. To evaluate the antitumor activity and therapeutic value of the TRAIL gene, we constructed adenoviral vectors expressing the human TRAIL gene (Ad.hTRAIL) and transferred them into malignant glioma cells in vitro and tumors in vivo, as an alternative to recombinant soluble TRAIL protein. The results show that TRAIL-sensitive glioma cells infected Ad.hTRAIL undergo apoptosis through the production and expression of TRAIL protein. The in vitro transfer elicited apoptosis, as demonstrated by the quantification of viable or apoptotic cells and by the analysis of cleavage of poly (ADP-ribose) polymerase. Furthermore, in vivo administration of Ad.hTRAIL at the site of tumor implantation suppressed the outgrowth of human glioma xenografts in SCID mice. These results further define Ad.hTRAIL as an anti-tumor therapeutic and demonstrate its potential use as an alternative approach to treatment for malignant glioma.
