Inhibitory Effects of ATP and Adenosine on Cholangiocarcinoma Cell Proliferation and Motility

Anticancer Res. 2017 Jul;37(7):3553-3561. doi: 10.21873/anticanres.11725.

Abstract

Background/aim: Inhibitory effects of extracellular nucleotides have been investigated in many types of cancers. Herein, we aimed to determine the effects of ATP and adenosine and their receptor profile on cholangiocarcinoma (CCA) cells.

Materials and methods: Two CCA and one immortalized cholangiocyte cell line were used. The effects of ATP and adenosine on cell proliferation and motility were examined by MTT and wound-healing/trans-well invasion assays, respectively. Purinergic receptor profiling was carried out by reverse transcription-polymerase chain reaction (RT-PCR).

Results: ATP and adenosine induced proliferation-inhibitory and motility-inhibitory effects in all cell lines tested. However, immortalized cholangiocytes showed resistance in proliferation inhibition. Several P2 receptors were commonly expressed in all cells, whereas no adenosine receptor was expressed. Furthermore, no synergistic effects of ATP and adenosine were observed in CCA cells.

Conclusion: ATP and adenosine had anti-proliferative and anti-motility effects in CCA cells, while there was a smaller effect on normal cholangiocytes. These data indicate the potential use of ATP and odenosine as a novel therapy for CCA.

Keywords: ATP; adenosine; cholangiocarcinoma; growth inhibition; motility inhibition; purinergic receptor.

MeSH terms

  • Adenosine / pharmacology*
  • Adenosine Triphosphate / pharmacology*
  • Bile Duct Neoplasms / drug therapy*
  • Bile Duct Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / metabolism*
  • Humans
  • Receptors, Purinergic P2 / metabolism
  • Signal Transduction / drug effects

Substances

  • Receptors, Purinergic P2
  • Adenosine Triphosphate
  • Adenosine