Ganoderma lucidum polysaccharides antagonize the suppression on lymphocytes induced by culture supernatants of B16F10 melanoma cells

J Pharm Pharmacol. 2011 May;63(5):725-35. doi: 10.1111/j.2042-7158.2011.01266.x.

Abstract

Objectives: Tumour cells produce factors such as interleukin 10 (IL-10), transforming growth factor β1 (TGF-β1) and vascular endothelial growth factor (VEGF) that suppress the function of immune cells or induce apoptosis of immune cells. One of the most important goals of tumour immunotherapy is to antagonize this suppression on immune cells. Ganoderma lucidum polysaccharides (Gl-PS) may have this potential. The purpose of this study was to determine the antagonistic effects of Gl-PS on the suppression induced by B16F10 melanoma cell culture supernatant (B16F10-CS) on lymphocytes.

Methods: Gl-PS was used on lymphocytes incubated with B16F10-CS. Enzyme-linked immunosorbent assay was used to determine the levels of IL-10, TGF-β1 and VEGF in B16F10-CS. The MTT assay was used to determine the proliferation of lymphocytes. Immunocytochemistry and Western blot assay were used to determine perforin and granzyme B production in lymphocytes.

Key findings: There were elevated levels of IL-10, TGF-β1 and VEGF in B16F10-CS. The lymphocyte proliferation, and perforin and granzyme B production in lymphocytes after induction with phytohemagglutinin, as well as lymphocyte proliferation in the mixed lymphocyte reaction, were suppressed by B16F10-CS. This suppression was fully or partially antagonized by Gl-PS.

Conclusions: B16F10-CS suppressed lymphocyte proliferation and perforin and granzyme B production in lymphocytes after induction with phytohemagglutinin, as well as lymphocyte proliferation in the mixed lymphocyte reaction. This suppression may be associated with elevated levels of immunosuppressive IL-10, TGF-β1 and VEGF in B16F10-CS. Gl-PS had antagonistic effects on the immunosuppression induced by B16F10-CS, suggesting the potential for Gl-PS in cancer immunotherapy.

MeSH terms

  • Animals
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Biological Products / therapeutic use
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Granzymes / biosynthesis
  • Immune Tolerance / drug effects*
  • Interleukin-10 / metabolism
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Count
  • Lymphocytes / drug effects*
  • Lymphocytes / metabolism
  • Melanoma, Experimental / drug therapy
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Perforin / biosynthesis
  • Plant Lectins
  • Polysaccharides / pharmacology*
  • Polysaccharides / therapeutic use
  • Reishi / chemistry*
  • Transforming Growth Factor beta1 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Biological Products
  • Plant Lectins
  • Polysaccharides
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A
  • Perforin
  • Interleukin-10
  • Granzymes