Polysaccharide from Lentinus edodes combined with oxaliplatin possesses the synergy and attenuation effect in hepatocellular carcinoma

Cancer Lett. 2016 Jul 28;377(2):117-25. doi: 10.1016/j.canlet.2016.04.037. Epub 2016 Apr 26.

Abstract

Despite the great progress in the treatment of hepatocellular carcinoma, combination chemotherapy is still the main choice of treatment for patients with unresectable metastatic or recurrent hepatocellular cancer. Lentinan, which has been used as an immunomodulator in the treatment of cancer, possesses anti-tumor activities. However, the mechanisms by which Lentinan inhibits hepatocellular carcinoma remain unknown. Our study showed that Lentinan has a significantly synergistic anti-tumor effect with oxaliplatin against HepG2 cells in vitro and in H22 tumor-bearing mice through the mitochondria pathway and for the inhibition of NF-κB, Stat3 and survivin signaling. Moreover, Lentinan moderated side effects induced by oxaliplatin. These findings suggested that Lentinan may be an ideal agent for the combination therapy of oxaliplatin against hepatocellular carcinoma.

Keywords: Apoptosis; Hepatocellular carcinoma; Lentinan; Oxaliplatin; Polysaccharide.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / toxicity
  • Apoptosis / drug effects*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Hep G2 Cells
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism
  • Lentinan / pharmacology*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • Mice, Inbred BALB C
  • Mitochondria, Liver / drug effects
  • Mitochondria, Liver / metabolism
  • NF-kappa B / metabolism
  • Organoplatinum Compounds / pharmacology*
  • Organoplatinum Compounds / toxicity
  • Oxaliplatin
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Survivin
  • Transfection
  • Tumor Burden / drug effects

Substances

  • Birc5 protein, mouse
  • Inhibitor of Apoptosis Proteins
  • NF-kappa B
  • Organoplatinum Compounds
  • Repressor Proteins
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Survivin
  • Oxaliplatin
  • Lentinan