✍ Scribed by Z. Gunnur Dikmen; Ginelle C. Gellert; Pakize Dogan; Heejeong Yoon; Young Bok Lee; Chang Ho Ahn; Jerry W. Shay
No coin nor oath required. For personal study only.
HIF‐1α 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‐1α is a potential target for the development of novel cancer therapeutics. This study was performed to determine the antitumoral efficacy of an antisense HIF‐1α 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. J. Cell. Biochem. 104: 985–994, 2008. © 2008 Wiley‐Liss, Inc.
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