Suppression of teratocarcinoma growth by soluble TRAIL gene driven by the progression-elevated gene-3 promoter

Abstract

A plasmid expressing the soluble tumor necrosis factor (TNF)-related apoptosis-inducing ligand sTRAIL amino acids 114-281 of TRAIL), driven by rat progression-elevated gene-3 (rPEG) promoter was constructed and evaluated. Transfection of embryonal carcinoma (EC) cells with the plasmid resulted in significant cellular apoptosis and elevated expression of death receptor 4 (DR4) and death receptor 5 (DR5). Direct intratumoral injection of DNA:liposome complexes suppressed tumor growth significantly and prolonged the survival of teratocarcinoma-bearing mice. Histological examination and serum analyses showed the absence of detectable toxicity in all examined tissues including liver. Our results demonstrate that sTRAIL gene expression driven by the rPEG promoter may enable effective gene therapy against teratocarcinoma.