Synergistic antitumor interactions between gemcitabine and clofarabine in human pancreatic cancer cell lines

Mol Med Rep. 2012 Mar;5(3):734-8. doi: 10.3892/mmr.2011.738. Epub 2011 Dec 23.

Abstract

Pancreatic cancer is a highly malignant disease, with a 5-year survival rate of less than 4%. Thus, new therapies for this deadly disease are urgently required. In this study, we sought to investigate whether combination treatments with gemcitabine and clofarabine result in synergistic cytotoxic effects against human pancreatic cancer cells. The type and extent of cytotoxic interactions between gemcitabine and clofarabine in three human pancreatic cancer cell lines were determined by MTT assays and standard isobologram analysis. The effects of the two agents on cell cycle distribution and apoptosis were determined by flow cytometry. Clofarabine significantly and synergistically enhanced gemcitabine cytotoxicities in all of the cell lines tested. This was accompanied by a nearly complete S phase arrest and synergistic induction of apoptosis (cooperativity index = 0.67). Combined treatment of gemcitabine and clofarabine resulted in synergistic cytotoxicities in vitro. Our results strongly suggest potential clinical benefits for using this drug combination to treat pancreatic cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Nucleotides / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Arabinonucleosides / pharmacology*
  • Cell Line, Tumor
  • Clofarabine
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Drug Synergism
  • Humans
  • Pancreatic Neoplasms / pathology
  • S Phase Cell Cycle Checkpoints / drug effects

Substances

  • Adenine Nucleotides
  • Antineoplastic Agents
  • Arabinonucleosides
  • Deoxycytidine
  • Clofarabine
  • gemcitabine