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

Z. Gunnur Dikmen, Ginelle C. Gellert, Pakize Dogan, Heejeong Yoon, Bok Lee Young, Ho Ahn Chang, Jerry W. Shay

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)985-994
Number of pages10
JournalJournal of Cellular Biochemistry
Volume104
Issue number3
DOIs
StatePublished - Jun 1 2008

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Tumors
Cells
Heterografts
Neoplasms
Animals
Genes
Bioluminescence
Imaging techniques
Histology
Ionizing radiation
Cell growth
Transcription
Cell Line
Luciferases
Ionizing Radiation
Reporter Genes
Lung Neoplasms
Prostatic Neoplasms
Homeostasis
Animal Models

Keywords

  • Bioluminescence imaging
  • Cancer
  • HIF-1α
  • Hypoxia
  • RX-0047

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Dikmen, Z. G., Gellert, G. C., Dogan, P., Yoon, H., Young, B. L., Chang, H. A., & Shay, J. W. (2008). In vivo and in vitro effects of a HIF-1α inhibitor, RX-0047. Journal of Cellular Biochemistry, 104(3), 985-994. https://doi.org/10.1002/jcb.21681

In vivo and in vitro effects of a HIF-1α inhibitor, RX-0047. / Dikmen, Z. Gunnur; Gellert, Ginelle C.; Dogan, Pakize; Yoon, Heejeong; Young, Bok Lee; Chang, Ho Ahn; Shay, Jerry W.

In: Journal of Cellular Biochemistry, Vol. 104, No. 3, 01.06.2008, p. 985-994.

Research output: Contribution to journalArticle

Dikmen, ZG, Gellert, GC, Dogan, P, Yoon, H, Young, BL, Chang, HA & Shay, JW 2008, 'In vivo and in vitro effects of a HIF-1α inhibitor, RX-0047', Journal of Cellular Biochemistry, vol. 104, no. 3, pp. 985-994. https://doi.org/10.1002/jcb.21681
Dikmen ZG, Gellert GC, Dogan P, Yoon H, Young BL, Chang HA et al. In vivo and in vitro effects of a HIF-1α inhibitor, RX-0047. Journal of Cellular Biochemistry. 2008 Jun 1;104(3):985-994. https://doi.org/10.1002/jcb.21681
Dikmen, Z. Gunnur ; Gellert, Ginelle C. ; Dogan, Pakize ; Yoon, Heejeong ; Young, Bok Lee ; Chang, Ho Ahn ; Shay, Jerry W. / In vivo and in vitro effects of a HIF-1α inhibitor, RX-0047. In: Journal of Cellular Biochemistry. 2008 ; Vol. 104, No. 3. pp. 985-994.
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