Effects of bicalutamide and 4OH-tamoxifen on androgen-regulated gene expression in the LNCaP cell line

Anticancer Res. 2012 Dec;32(12):5323-9.

Abstract

Background: Bicalutamide (BIC) is an alternative treatment to castration for advanced prostate cancer. Breast events are common adverse effects which can be effectively prevented by the concurrent administration of tamoxifen, a selective estrogen receptor modulator.

Materials and methods: We investigated the effects of BIC, 4-hydroxy Tamoxifen (4OHT), the active metabolite of tamoxifen, and their combination on the expression of a panel of genes implicated in prostate cancer development and progression in LNCaP cells stimulated with dihydrotestosterone.

Results: Our findings confirm the anti-proliferative activity of BIC on LNCaP cell growth but also show the down-regulating function of this anti-androgen on the expression of genes involved in tumor proliferation and invasion [cyclins, caspases, epidermal growth factor (EGF)]. The combination with 4OHT exerts a synergistic effect on the downregulation of some genes involved in prostate cancer progression.

Conclusion: The observation that the expression of several genes [such as B-cell lymphoma-2 (BCL2), myelocytomatosis oncogene (MYC), caspases] is modulated midly-to-moderately, after 4OHT addition suggests that this combined approach in the clinical setting should be further investigated through appropriate trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / physiology*
  • Anilides / administration & dosage
  • Anilides / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Kallikreins / biosynthesis
  • Male
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / genetics
  • Nitriles / administration & dosage
  • Nitriles / pharmacology*
  • Prostate-Specific Antigen / biosynthesis
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics*
  • Tamoxifen / administration & dosage
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / pharmacology
  • Tosyl Compounds / administration & dosage
  • Tosyl Compounds / pharmacology*

Substances

  • Androgens
  • Anilides
  • Nitriles
  • Tosyl Compounds
  • Tamoxifen
  • afimoxifene
  • bicalutamide
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen