Synergistic antitumor effect of polysaccharide from Lachnum sp. in combination with cyclophosphamide in hepatocellular carcinoma

Carbohydr Polym. 2018 Sep 15:196:33-46. doi: 10.1016/j.carbpol.2018.05.006. Epub 2018 May 3.

Abstract

Combination therapy with chemotherapeutics is attracting increasing attention as an important treatment option for hepatocellular carcinoma (HCC) due to its complex pathological characteristics. In this study, as a new therapy strategy, combination treatment of LEP-2a (a non-toxic polysaccharide from Lachnum sp.) with cyclophosphamide (CTX) was investigated. Results showed that combination treatment with LEP-2a and CTX processed a significantly synergistic anti-tumor effect in H22 tumor-bearing mice through Fas/FasL mediated caspase-dependent death pathway and mitochondria apoptosis pathway. Moreover, our study indicated that LEP-2a played a crucial role in enhancement of immune response, inhibition of tumor angiogenesis and down-regulation of survival associated proteins. Notably, side effects induced by CTX were relieved after LEP-2a treatment. These results support the conception that LEP-2a has the potential as an ideal adjuvant agent for a more effective combination therapy with CTX against HCC.

Keywords: Cyclophosphamide; Hepatocellular carcinoma; Lachnum exopolysaccharide; Synergistic anti-tumor effect.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Ascomycota / chemistry*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclophosphamide / pharmacology*
  • Drug Synergism
  • Fungal Polysaccharides / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Liver Neoplasms / pathology*
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Fungal Polysaccharides
  • Cyclophosphamide