Abstract 2661: The role of HIF-1 protein on the radiosensitizing effect of difluorodeoxyuridine, the main metabolite of gemcitabine, under normoxic and anoxic conditions

• Published in: Cancer research (Chicago, Ill.) Ill.), 2011-04, Vol.71 (8_Supplement), p.2661-2661
• Main Authors: Pauwels, Bea, Wouters, An, Vermorken, Jan B., Ides, Johan, Deschoolmeester, Vanessa, Lambrechts, Hilde AJ, Pattyn, Greet GO, Meijnders, Paul, Pauwels, Patrick, Williams, Kaye J., Peeters, Marc, Lardon, Filip
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-2661

It is known that gemcitabine and difluorodeoxyuridine (dFdU) have radiosensitizing properties. It has become evident that solid tumors often contain hypoxic regions and that this is one of the causes of resistance or decreased sensitivity to cancer therapy. In hypoxic conditions, the transcription factor, hypoxia-inducible factor-1 (HIF-1), is upregulated. HIF-1 is responsible for the cellular and adaptive responses of tumors to survive in hypoxic conditions. Recently, it has been demonstrated that gemcitabine retains its radiosensitizing potential under hypoxia. In the present study, the radiosensitizing potential of dFdU under anoxic conditions is investigated as well as the role of HIF-1 protein. In order to explore the role of HIF-1, human tumor cell lines included in this study were MDA-MB-231 (breast adenocarcinoma cell line, wt HIF-1), MDA-MB-231 DN-HIF (transfected with dominant-negative HIF-1α) and MDA-MB-231 EV (empty vector transfected control). Anoxic conditions (