The hTERT Promoter Enhances the Antitumor Activity of an Oncolytic Adenovirus under a Hypoxic Microenvironment

摘要: Hypoxia is a microenvironmental factor that contributes to the invasion, progression and metastasis of tumor cells. Hypoxic cells often show more resistance conventional chemoradiotherapy than normoxic cells, suggesting requirement novel antitumor therapies efficiently eliminate hypoxic We previously generated tumor-specific replication-competent oncolytic adenovirus (OBP-301: Telomelysin), in which human telomerase reverse transcriptase (hTERT) promoter drives viral E1 expression. Since activity hTERT gene has been shown be upregulated by hypoxia, we hypothesized that, under conditions, effect OBP-301 with would efficient wild-type 5 (Ad5). In this study, investigated effects Ad5 against cancer (20% oxygen) or (1% condition. condition induced nuclear accumulation hypoxia-inducible factor-1α upregulation The cytopathic was significantly higher Consistent their activity, replication OBP-301-mediated E1A expressed within areas xenograft tumors mice. These results suggest mediated through hypoxia-mediated activation promoter. Regulation adenoviruses promising strategy, not only for induction oncolysis, but also elimination