Endothelin A receptor blockade does not alter PSA secretion in prostate cancer cell lines

Prostate. 2004 Aug 1;60(3):175-7. doi: 10.1002/pros.20116.

Abstract

Background: Some men treated with atrasentan (ABT-627), an endothelin A (ETA) receptor inhibitor, had declines in their serum PSA levels. It is our hypothesis that this decrease is due to anti-tumoral activity and not a reduction in PSA secretion at the cellular level.

Methods: Two PSA secreting prostate cancer cell lines (LAPC4 and LNCaP) were treated with atrasentan and an ETB receptor antagonist (A192621) in varying concentrations (10(-6)-10(-10) M) and PSA levels were measured in the culture media.

Results: LNCaP and LAPC4 cells both express ETA receptors. Neither the ETA or ETB antagonist altered PSA secretion, while addition of DHT, a positive control, produced a marked increase in PSA secretion.

Conclusions: Blockade of the ETA receptor does not affect the secretion of PSA in prostate cancer cell lines.

MeSH terms

  • Atrasentan
  • Endothelin A Receptor Antagonists*
  • Endothelin-1 / antagonists & inhibitors
  • Humans
  • Male
  • Prostate-Specific Antigen / metabolism*
  • Prostatic Neoplasms / pathology*
  • Pyrrolidines / pharmacology
  • Receptor, Endothelin A / physiology*
  • Tumor Cells, Cultured

Substances

  • A 192621
  • Endothelin A Receptor Antagonists
  • Endothelin-1
  • Pyrrolidines
  • Receptor, Endothelin A
  • Prostate-Specific Antigen
  • Atrasentan