The synergistic in vitro and in vivo antitumor effect of combination therapy with salinomycin and 5-fluorouracil against hepatocellular carcinoma

PLoS One. 2014 May 9;9(5):e97414. doi: 10.1371/journal.pone.0097414. eCollection 2014.

Abstract

Hepatocellular carcinoma (HCC) is one of the few cancers in which a continuous increase in incidence has been observed over several years. Drug resistance is a major problem in the treatment of HCC. In the present study, we used salinomycin (Sal) and 5-fluorouracil (5-FU) combination therapy on HCC cell lines Huh7, LM3 and SMMC-7721 and nude mice subcutaneously tumor model to study whether Sal could increase the sensitivity of hepatoma cells to the traditional chemotherapeutic agent such as 5-FU. The combination of Sal and 5-FU resulted in a synergistic antitumor effect against liver tumors both in vitro and in vivo. Sal reversed the 5-FU-induced increase in CD133(+) EPCAM(+) cells, epithelial-mesenchymal transition and activation of the Wnt/β-catenin signaling pathway. The combination of Sal and 5-FU may provide us with a new approach to reverse drug resistant for the treatment of patients with HCC.

MeSH terms

  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Carcinoma, Hepatocellular / drug therapy*
  • Cell Line
  • Colony-Forming Units Assay
  • DNA Primers / genetics
  • Drug Synergism
  • Drug Therapy, Combination / methods*
  • Epithelial-Mesenchymal Transition / drug effects
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use*
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / drug therapy*
  • Mice
  • Pyrans / pharmacology
  • Pyrans / therapeutic use*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Wnt Signaling Pathway / drug effects

Substances

  • DNA Primers
  • Pyrans
  • salinomycin
  • Fluorouracil

Grants and funding

This research was funded by National Nature Science Foundation of China (No. 81302788). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.