Polysaccharide-K augments docetaxel-induced tumor suppression and antitumor immune response in an immunocompetent murine model of human prostate cancer

Cynthia A. Wenner, Mark R. Martzen, Hailing Lu, Michael R Verneris, Hongbo Wang, Joel W. Slaton

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Advanced castration-resistant prostate cancer has high mortality rates and limited treatment options. Novel therapies are needed to better contend with this disease. Polysaccharide-K® (PSK), an extract of the mushroom Trametes versicolor, has immunomodulatory and tumor suppressive activities. PSK is used in Asia as a cancer immunotherapy. However, its benefit in combination with taxanes for prostate cancer is unknown. We examined whether PSK would enhance docetaxel-induced apoptosis and augment anti-tumor immune responses in orthotopic tumors using transgenic adenocarcinoma of the mouse prostate (TRAMP)-C2-bearing mice. Combining PSK with docetaxel induced significantly higher tumor suppression than either treatment alone (p<0.05), including a reduction in tumor proliferation and enhanced apoptosis. Combined PSK and docetaxel treatment led to a lower decrease in number of white blood cells than docetaxel alone, an effect accompanied by increased numbers of tumor-infiltrating CD4 + and CD8 + T cells. PSK with or without docetaxel significantly enhanced mRNA expression of IFN-γ compared to control, but did not significantly alter T-regulatory FoxP3 mRNA expression in tumors. PSK also augmented docetaxel-induced splenic natural killer cell cytolytic activity against YAC-1 target cells (p=0.045). This study is the first to show that PSK enhances docetaxel-induced prostate cancer tumor suppression, apoptosis and antitumor responses.

Original languageEnglish (US)
Pages (from-to)905-913
Number of pages9
JournalInternational Journal of Oncology
Volume40
Issue number4
DOIs
StatePublished - Apr 1 2012

Keywords

  • Apoptosis
  • Docetaxel
  • Natural killer cell
  • Polysaccharide-K
  • Prostate cancer

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