Atorvastatin enhances radiosensitivity in hypoxia-induced prostate cancer cells related with HIF-1α inhibition

Biosci Rep. 2017 Aug 21;37(4):BSR20170340. doi: 10.1042/BSR20170340. Print 2017 Aug 31.

Abstract

Hypoxia could enhance radioresistance in prostate cancer cells through up-regulating HIF-1α, which could be inhibited by statins in several cancer cells. However, this effect of statins in prostate cancer remains unclear. In the present study, we aim to investigate the effect of atorvastatin on HIF-1α expression and radiosensitivity in prostate cancer cells. The hypoxia-induced human prostate cancer PC3 cells were generated by incubating with 5% O2 for 24 h. The cell viability and apoptosis were respectively analyzed by cell counting kit-8 (CCK-8) assay and flow cytometry. The HIF-1α protein expression was assessed by Western blotting. HIF-1α expression in PC3 cells was significantly increased after incubating with 5% O2 for 24 h. The viability of hypoxia-induced PC3 cells was inhibited by a higher dose of irradiation than control cells. The viability of hypoxia-induced PC3 cells were inhibited by astorvastatin with a higher concentration than control cells. Astorvastatin reduced the HIF-1α protein expression in hypoxia-induced PC3 cells, and induced apoptosis of both control and hypoxia-induced cells with and without irradiation. Atorvastatin could enhance radiosensitivity in hypoxia-induced prostate cancer cells, which may be related with inhibition of HIF-1α protein.

Keywords: Atorvastatin; HIF-1α; prostate cancer; radiosensitivity.

MeSH terms

  • Apoptosis / drug effects
  • Atorvastatin / pharmacology*
  • Cell Hypoxia
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Male
  • Prostatic Neoplasms / metabolism*
  • Radiation Tolerance / drug effects*

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Atorvastatin