Mitotic disruption and reduced clonogenicity of pancreatic cancer cells in vitro and in vivo by tumor treating fields

Pancreatology. Jan-Feb 2014;14(1):54-63. doi: 10.1016/j.pan.2013.11.009. Epub 2013 Dec 4.

Abstract

Objectives: Tumor Treating Fields (TTFields) are a non-invasive cancer treatment modality approved for the treatment of patients with recurrent glioblastoma. The present study determined the efficacy and mechanism of action of TTFields in preclinical models of pancreatic cancer.

Methods: The effect of TTFields in vitro was assessed using cell counts, clonogenic assays, cell cycle analysis and analysis of mitotic figures. The effect in vivo effect was studied in the PC1-0 hamster pancreatic cancer model.

Results: Application of TTFields in vitro showed a significant decrease in cell count, an increase in cell volume and reduced clonogenicity. Further analysis demonstrated significant increase in the number of abnormal mitotic figures, as well as a decrease in G2-M cell population. In hamsters with orthotopic pancreatic tumors, TTFields significantly reduced tumor volume accompanied by an increase in the frequency of abnormal mitotic events. TTFields efficacy was enhanced both in vitro and in vivo when combined with chemotherapy.

Conclusions: These results provide the first evidence that TTFields serve as an effective antimitotic treatment in preclinical pancreatic cancer models and have a long term negative effect on cancer cell survival. These results make TTFields an attractive candidate for testing in the treatment of patients with pancreatic cancer.

Keywords: Anti-mitotic; Cell volume; Clonogenic assay; TTFields.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Size / drug effects
  • Combined Modality Therapy
  • Cricetinae
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Electricity
  • Humans
  • Male
  • Mesocricetus
  • Mitosis / drug effects*
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / pathology*
  • Treatment Outcome
  • Tumor Stem Cell Assay

Substances

  • Deoxycytidine
  • gemcitabine