Exploring the Role of Enzalutamide in Combination with Radiation Therapy: An In Vitro Study

Anticancer Res. 2018 Jun;38(6):3487-3492. doi: 10.21873/anticanres.12619.

Abstract

Background/aim: Androgen receptor plays a key role in prostate cancer development and is a causative agent of its radio-resistance. The present study investigated the potential radio-sensitizing effect of enzalutamide, a second-generation anti-androgen, in human prostate cancer cells.

Materials and methods: The radio-sensitizing effect of enzalutamide was assessed in the androgen-dependent LNCaP cells and the androgen-independent PC3 cells by clonogenic assay and γ-H2AX assay.

Results: Enzalutamide-treated LNCaP cells showed a significant decrease of cell survival at all radiation doses tested. An increased number of γ-H2AX-positive nuclei was observed, suggesting a possible impairment of the DNA repair machinery. Conversely, enzalutamide did not exhibit a significant radio-sensitizing effect on PC3 cells.

Conclusion: The combination of enzalutamide with ionizing radiation significantly improves radio-sensitivity of hormone-dependent LNCaP cells. Translated in the clinical practice, our results may help to find additional strategies to improve effectiveness of radiotherapy.

Keywords: Prostate cancer; androgen receptor; enzalutamide; ionizing radiation; γ-H2AX.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Benzamides
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Proliferation / radiation effects*
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Dose-Response Relationship, Radiation
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / radiation effects
  • Histones / metabolism
  • Humans
  • Male
  • Nitriles
  • Phenylthiohydantoin / analogs & derivatives*
  • Phenylthiohydantoin / pharmacology
  • Prostatic Neoplasms / pathology
  • Radiation-Sensitizing Agents / pharmacology*

Substances

  • Antineoplastic Agents
  • Benzamides
  • H2AX protein, human
  • Histones
  • Nitriles
  • Radiation-Sensitizing Agents
  • Phenylthiohydantoin
  • enzalutamide