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J Cell Biochem. 2008 Jun 1;104(3):985-94. doi: 10.1002/jcb.21681.

In vivo and in vitro effects of a HIF-1alpha inhibitor, RX-0047.

Author information

1
Department of Biochemistry, Faculty of Medicine, University of Hacettepe, 06100 Sihhiye, Ankara, Turkey. gunnur@hacettepe.edu.tr

Abstract

HIF-1alpha plays a major role in activating gene transcription and is important for maintaining homeostasis under hypoxic conditions. Since tumors are often in a hypoxic state, HIF-1alpha is a potential target for the development of novel cancer therapeutics. This study was performed to determine the antitumoral efficacy of an antisense HIF-1alpha inhibitor, RX-0047 on different human cancer cell lines (MDA-MB 231, HME50-T, PC-3, Panc-1 and A549) in vitro. A549 lung cancer and PC-3 prostate cancer cells containing a luciferase gene reporter were used for in vivo xenograft animal models. Progressive tumor development was quantified using live animal BLI (bioluminescence imaging) in addition to ex vivo imaging and histology. All cell lines tested were sensitive to inhibition of cell growth with 10 nM and higher ranges of RX-0047, additionally RX-0047 sensitizes cells to ionizing radiation treatments. Finally, RX-0047 (30 mg/kg) inhibited the formation of human lung metastasis in xenograft mouse models and reduced tumor size in flank models.

PMID:
18275063
PMCID:
PMC3375689
DOI:
10.1002/jcb.21681
[Indexed for MEDLINE]
Free PMC Article

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