Modulation of radiosensitivity of DU145 prostate carcinoma cells by simvastatin

J Cancer Res Clin Oncol. 2023 Jul;149(8):4509-4514. doi: 10.1007/s00432-022-04364-9. Epub 2022 Sep 21.

Abstract

Purpose: To investigate antiproliferative effects of simvastatin in combination with ionizing radiation on DU145 prostate cancer cells and its influence on cellular HMG-CoA-reductase levels.

Methods: Proliferative responses of DU145 cells were estimated by means of a clonogenic assay or the crystal violet procedure. HMG-CoA-reductase levels were measured by western blot analysis.

Results: The antiproliferative effects of simvastatin and radiation are dependent on simvastatin dose, radiation dose and treatment time. In vitro treatment of DU145 cells with simvastatin induced HMG-CoA-reductase levels.

Conclusion: Ionizing radiation more profoundly reduces proliferation as compared to simvastatin exposure, while the combined application of both modalities is synergistic. The inhibition of CoA-reductase may contribute to these effects.

Keywords: DU145; HMG-CoA-reductase; Prostate cancer; Radiosensitivity; Simvastatin.

MeSH terms

  • Carcinoma*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Male
  • Prostate / pathology
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / pathology
  • Prostatic Neoplasms* / radiotherapy
  • Radiation Tolerance
  • Simvastatin / pharmacology

Substances

  • Simvastatin
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors