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Title 

Oncolytic effects of adenovirus mutant capable of replicating in hypoxic and normoxic regions of solid tumor

Authors 

Won-Kyung ChoY R SeongY H LeeM J KimKyung Sun HwangJin Sang YooSee Young ChoiCho Rok JungDong Soo Im

Publisher 

Elsevier

Issue Date 

2004

Citation 

Molecular Therapy, vol. 10, no. 5, pp. 938-949

Keywords 

adenovirushypoxiaoncolytictumorbreast tumorprostate tumorsolid tumortumor cell culturetumor growthtumor vascularization

Abstract 

Solid tumors contain normoxic and hypoxic regions depending on the distance from the capillary. Normal cells may also be exposed to hypoxia under certain physiological conditions. Tumor hypoxia has been shown to associate strongly with tumor propagation and malignant progression. Hypoxia-inducible factor (HIF)-1α is stable under hypoxia and induces transcription of target genes by binding to the hypoxia-response element (HRE). Here we investigated the oncolytic effects of a novel adenovirus mutant with a deleted E1B55 gene (Ad.δ55.HRE), in which the expression of E1A, which is essential for adenoviral replication, is regulated under the control of an HRE-expression system. Ad.δ55.HRE expressed E1A under normoxia and more E1A under hypoxia and exhibited oncolytic effects on various cultured tumor cells, but its cytotoxic effect is relatively attenuated in normal fibroblast cells under normoxic and hypoxic conditions. Ad.δ55.HRE lysed Huh-7 hepatoma cells stably expressing HIF-1α more effectively compared to parental cells. Ad.δ55.HRE treatment exhibited significant antitumor activity in PC-3 prostate- and MDA-MB-435 breast tumor-bearing nude mice in which HIF-1α protein was immunohistochemically detected. The E1A and hexon proteins of adenovirus were immunostained in MDA-MB-435 xenografts after Ad.δ55.HRE treatment, suggestive of viral replication. Our results suggest that Ad.δ55.HRE may be useful for the treatment of solid tumors.

ISSN 

1525-0016

Link 

http://dx.doi.org/10.1016/j.ymthe.2004.07.023

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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