Down-regulation of HIF-1α by oncolytic reovirus infection independently of VHL and p53

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Title
Down-regulation of HIF-1α by oncolytic reovirus infection independently of VHL and p53
Author(s)
I R Cho; Sang Seok Koh; Hye Jin Min; E H Park; S Ratakorn; B H Jhun; S H Jeong; Y H Yoo; H D Youn; R N Johnston; Y H Chung
Bibliographic Citation
Cancer Gene Therapy, vol. 17, no. 5, pp. 365-372
Publication Year
2010
Abstract
Many oncolytic viruses are currently being tested as potential cancer therapeutic agents. To be effective, these viruses must replicate and propagate efficiently through the tumor mass. However, it is possible that the hypoxia that characterizes many tumors may be an obstacle to viral therapy because of its inhibition of viral replication and propagation. We, therefore, decided to test how oncolytic reovirus and its target cells respond to hypoxia. We found that reovirus infection suppresses hypoxia inducible factor (HIF)-1α protein levels (but not transcript abundance) in colon cancer HCT116 cells under CoCl 2 or hypoxia. Reovirus infection was able to reduce HIF-1α levels in both von Hippel Lindau (VHL)\renal carcinoma A498 and p53\HCT116 cells, indicating that the decrease of HIF-1α mediated by reovirus requires neither VHL nor p53 proteins. However, treatment with the inhibitor MG132 restored HIF-1α levels, suggesting that reovirus-induced HIF-1α decrease needs proteosomal activity. A498 VHL\cells with constitutive expression of HIF-1α were relatively resistant to reovirus-induced apoptosis when compared with A498 VHL\cells. However, we found that the use of YC-1 to target HIF-1α promoted reovirus-induced apoptosis in A498 VHL\cells. Accordingly, we propose that reovirus may be used together with YC-1 as a potential therapeutic agent against chemoresistant or radioresistant tumors that are hypoxic and show increased levels of HIF-1α.
Keyword
Hypoxic inducible factor-1aRenal carcinomaReovirusVon Hippel Lindau (VHL)YC-1
ISSN
0929-1903
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/cgt.2009.84
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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