Octreotide in combination with AT-101 induces cytotoxicity and apoptosis through up-regulation of somatostatin receptors 2 and 5 in DU-145 prostate cancer cells

Tumour Biol. 2016 Apr;37(4):4939-44. doi: 10.1007/s13277-015-4331-0. Epub 2015 Nov 3.

Abstract

Prostate cancer (PCa) is the most common type of cancer among males. Although survival rate of early-stage PCa is high, treatment options are very limited for recurrent disease. In this study, the possible synergistic cytotoxic and apoptotic effect of octreotide in combination with AT-101 was investigated in DU-145 hormone and drug refractory prostate cancer cell line. To enlighten the action mechanisms of the combination treatment, expression levels of somatostatin receptors 2 and 5 (SSTR2 and SSTR5) were also investigated. Cell viability was measured by XTT assay. Apoptosis was assessed through DNA fragmentation analysis and caspase 3/7 assay. mRNA and protein levels of SSTR2 and SSTR5 were evaluated by qRT-PCR and western blot analysis, respectively. Octreotide in combination with AT-101 inhibited cell viability and induced apoptosis synergistically in DU-145 cells as compared to any agent alone. Combination treatment increased both SSTR2 and SSTR5 mRNA and protein levels in DU-145 cells. The data suggest that this combination therapy may be a good candidate for patients with advanced metastatic PCa do not respond to androgen deprivation.

Keywords: AT-101; Apoptosis; Cell viability; Octreotide; SSTR2 and SSTR5.

MeSH terms

  • Androgens / metabolism
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Drug Synergism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gossypol / administration & dosage
  • Gossypol / analogs & derivatives
  • Humans
  • Male
  • Octreotide / administration & dosage
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Receptors, Somatostatin / biosynthesis*
  • Receptors, Somatostatin / genetics

Substances

  • Androgens
  • Receptors, Somatostatin
  • somatostatin receptor 5
  • somatostatin receptor 2
  • Gossypol
  • Octreotide
  • gossypol acetic acid