Experimental therapy against ovarian cancer by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene driven by human telomerase reverse transcriptase (hTERT) promoter

摘要

TRAIL functions as a soluble cytokine killing various cancer cells with limited toxicity to most normal cells. Human telomerase reverse transcriptase (hTERT) promoter is known to selectively drive transgene expression in many human cancer cells. In this study, we aimed to determine whether the hTERT promoter could efficiently mediate more specific TRAIL gene therapy in ovarian cancer cells. We demonstrated that?green fluorescent protein?(GFP)?expression driven by the hTERT promoter was observed in several ovarian cancer cells, but not in normal epithelial cells. hTERT promoter activity was comparable to that of Cytomegalovirus (CMV) promoter in ovarian cancer SKOV3 cells, as judged by GFP expression level detected by real-time polymerase chain reaction (PCR) and flow cytometry, as well as TRAIL expression detected by western blot. Both hTERT-TRAIL and CMV-TRAIL constructs displayed comparable proliferation inhibition and induced cell apoptosis in ovarian cancer SKOV3 cells, and both exerted effects that are statistically different from control group. Moreover,?in vivo?studies indicated that intratumoral administration of these vectors significantly suppressed the growth of xenograft tumors, compared with control group. These data demonstrated that hTERT promoter can efficiently and specifically drive TRAIL gene expression in ovarian cancer SKOV3 cells, thus specifically induce apoptosis in these cells and reduced cancer growth?in vivo.