Synergistic effects of pemetrexed and amrubicin in non-small cell lung cancer cell lines: Potential for combination therapy

Cancer Lett. 2014 Feb 1;343(1):74-9. doi: 10.1016/j.canlet.2013.09.019. Epub 2013 Oct 15.

Abstract

The purpose is to examine the synergistic effect of pemetrexed (PEM) and amrubicin (AMR) on the proliferation of lung cancer cell lines. In vitro, dose-dependent synergistic effects of concurrent PEM and AMRol, which is an active metabolite of AMR were observed in A549 and H460 cells. In real-time RT-qPCR analysis and western blotting, expression of the target enzymes of PEM were suppressed in cells treated with amrubicinol alone. In vivo, AMR/PEM treatment also showed synergistic antitumor activity both in A549-bearing and H520-bearing mice. PEM and AMR work synergistically to inhibit the proliferation of several different lung cancer cell lines.

Keywords: Amrubicin; Non-small cell lung cancer; Pemetrexed; Thymidylate synthase.

MeSH terms

  • Animals
  • Anthracyclines / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Female
  • Glutamates / administration & dosage*
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives*
  • Humans
  • Inhibitory Concentration 50
  • Lung Neoplasms / drug therapy*
  • Mice
  • Mice, Inbred BALB C
  • Pemetrexed
  • Time Factors

Substances

  • Anthracyclines
  • Glutamates
  • Pemetrexed
  • Guanine
  • amrubicin