Antitumor activity of TRAIL recombinant adenovirus in human malignant glioma cells.
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.
Kim
Ki-Uk
KU
Brain Tumor Research, Dong-A University College of Medicine, Busan, Korea.
Seo
Su-Yeong
SY
Heo
Ki-Young
KY
Yoo
Young-Hyun
YH
Kim
Hye-Jin
HJ
Lee
Hyeong-Sik
HS
Choi
Sun-Seob
SS
Hwang
Tae-Ho
TH
Lee
Hye-Jeong
HJ
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D053221:TNF-Related Apoptosis-Inducing Ligand; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha