The combination of docetaxel and the somatostatin analogue lanreotide on androgen-independent docetaxel-resistant prostate cancer: experimental data

BJU Int. 2008 Aug 5;102(5):622-7. doi: 10.1111/j.1464-410X.2008.07706.x. Epub 2008 May 20.

Abstract

Objective: To evaluate the effects of the association between docetaxel and the somatostatin analogue lanreotide on the androgen-independent prostate cancer cell line PC3, either sensitive or made resistant to docetaxel (PC3R), as new drugs and new combinations have promising clinical activity in hormone-refractory prostate cancer.

Materials and methods: We examined the effect of docetaxel and lanreotide on cell proliferation, with analysis of the mitogen-activated protein kinase pathway and expression of cell-cycle regulatory proteins.

Results: Combined treatment with docetaxel and lanreotide inhibited PC3 cell growth in vitro through an enhanced induction of cell death, compared with treatment with either agent alone; this result was particularly evident on PC3R cells. The results suggested that lanreotide could act as a P glycoprotein inhibitor in PC3R cells.

Conclusion: The present results provide a promising therapeutic approach for using somatostatin analogues in hormone-refractory prostate cancer, in which lanreotide could interact with docetaxel in PC3R cells, with possible explanatory mechanisms which involve P glycoprotein-mediated docetaxel resistance.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Blotting, Western
  • Cell Line, Tumor
  • Docetaxel
  • Drug Evaluation
  • Drug Resistance, Neoplasm
  • Humans
  • Male
  • Mitogen-Activated Protein Kinase Kinases / drug effects
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Peptides, Cyclic / administration & dosage
  • Prostatic Neoplasms / drug therapy*
  • Signal Transduction / drug effects
  • Somatostatin / administration & dosage
  • Somatostatin / analogs & derivatives
  • Taxoids / administration & dosage

Substances

  • Peptides, Cyclic
  • Taxoids
  • lanreotide
  • Docetaxel
  • Somatostatin
  • Mitogen-Activated Protein Kinase Kinases