title: In vivo and in vitro effects of a HIF-1alpha inhibitor, RX-0047.
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.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Hacettepe, 06100 Sihhiye, Ankara, Turkey. gunnur@hacettepe.edu.tr
authors.forename: Z Gunnur
authors.initials: ZG
authors.lastname: Dikmen
authors.forename: Ginelle C
authors.initials: GC
authors.lastname: Gellert
authors.forename: Pakize
authors.initials: P
authors.lastname: Dogan
authors.forename: Heejeong
authors.initials: H
authors.lastname: Yoon
authors.forename: Young Bok
authors.initials: YB
authors.lastname: Lee
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Ahn
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Shay
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D017930:Genes, Reporter; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D008956:Models, Chemical; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009841:Oligonucleotides / Q000494:pharmacology*; D014158:Transcription, Genetic
chemical_list: D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009841:Oligonucleotides; C531306:RX 0047