Effect of radiation and ibuprofen on normoxic renal carcinoma cells overexpressing hypoxia-inducible factors by loss of von Hippel-Lindau tumor suppressor gene function

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Sanjeewani T PalayoorC Norman Coleman

Abstract

Tumor hypoxia is a major limiting factor for radiation therapy. Hypoxia-inducible factors (HIFs) are overexpressed in several human cancers and are considered prognostic markers and potential targets for cancer therapy. The purpose of the present study was to investigate the impact of HIFs on radiosensitivity. Renal clear cell carcinoma (RCC) cell lines overexpressing HIFs under normoxic conditions because of inactivation of von Hippel-Lindau tumor suppressor gene function (VHL-ve) and their matched pairs in which overexpression of HIFs was abolished by expression of functional VHL (VHL+ve) were irradiated. Radiosensitivity was determined by clonogenic assay. HIF and VHL protein levels were evaluated by Western blot analysis. RCC cells were also treated with ibuprofen, a radiosensitizer and HIF inhibitor in prostate cancer cells. The effect of ibuprofen on radiosensitization and HIF and VHL proteins was compared in RCC matched-pair cell lines. The data showed only small differences in the radiosensitivity between the cells overexpressing HIFs and cells with basal HIF levels. The dose-modifying factors for C2, 786-0, and A498 RCC cells were 1.14, 1.14 and 1.15, respectively. Radiation did not alter HIF or VHL protein levels. Ibu...Continue Reading

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Citations

Jun 7, 2012·Journal of Cardiovascular Pharmacology·Sanjeewani T PalayoorC Norman Coleman
Sep 2, 2011·Chemical & Pharmaceutical Bulletin·Heidi Rose BokeschTawnya Carlene McKee
Jun 10, 2014·Cancer Cell International·Defeng QiWeidong Ji
Aug 30, 2008·International Journal of Cancer. Journal International Du Cancer·Sanjeewani T PalayoorC Norman Coleman
May 25, 2011·Journal of Gynecologic Oncology·Min Kyu KimByoung-Gie Kim
Dec 20, 2011·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Mareike StröferReinhard Depping
May 10, 2005·Clinical and Diagnostic Laboratory Immunology·J L FormentoG Milano
Oct 18, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Murali GururajanLeland W K Chung
Oct 6, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sanjeewani T PalayoorC Norman Coleman

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