Octreotide reverses the resistance of A2780/Pacliaxel ovarian cancer cell line to paclitaxel chemotherapy in vitro

J Cancer Res Ther. 2016 Apr-Jun;12(2):657-62. doi: 10.4103/0973-1482.151861.

Abstract

Objective: To study the anti-tumor effects of octreotide on A2780/Taxol ovarian cancer cells in vitro, and further explore its potential molecular mechanism.

Materials and methods: Immunocytochemistry was performed to determine the expression of SSTR2 on A2780/Taxol cells. Octreotide at different concentrations (0, 1.25, 2.5, 5.0, 10.0, and 20.0 nmol/ml) were administrated to A2780/Taxol cells in vitro. CCK-8 assay was used to measure the effects on cell proliferation, and the cytometry of octreotide determined the cell apoptosis. The expressions of SSTR2 MDR1, and vascular endothelial growth factor (VEGF) messenger ribonucleic acid (mRNA) were investigated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay and the expressions of the above protein were investigated after A2780/Taxol was treated with octreotide for 48 hours by western blot in vitro.

Results: Positive expression of SSTR2 was observed on the membrane of A2780/Taxol cells. The proliferation of A2780/Taxol cells was gradually inhibited with increasing octreotide concentration in a concentration-dependent and time-dependent manner. Meanwhile, flow cytometry data demonstrated the octreotide-induced cell apoptosis. The results of SSTR2 mRNA suggested that there was no significant difference between each concentration group of octreotide (P > 0.05). Compared with the control group, both the MDR1 and VEGF mRNA decreased in a dose-dependent manner following 48 hours of treatment of octreotide (P < 0.05). The results of western blot showed that octreotide decreased the expressions of SSTR2, MDR1, and VEGF protein in a dose-dependent manner (P < 0.05).

Conclusions: Octreotide significantly inhibits ovarian cancer's proliferation and promotes its apoptosis via the cell surface expression of SSTR2. It could be used as a new targeted drug for treatment of ovarian cancer.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / analysis
  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / physiology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Immunohistochemistry
  • Octreotide / pharmacology*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Paclitaxel / pharmacology*
  • Receptors, Somatostatin / analysis
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / physiology

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Receptors, Somatostatin
  • SSTR2 protein, human
  • Paclitaxel
  • Octreotide