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, Cynthia A Wenner, Mark R Martzen, Hailing Lu, Michael R Verneris, Hongbo Wang, Joel W Slaton
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.
Figures
References
- Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–2917.
- Lassi K, Dawson NA. Update on castrate-resistant prostate cancer: 2010. Curr Opin Oncol. 2010;22:263–267.
- Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351:1513–1520.
- Tannock IF, De Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502–1512.
- Gueritte-Voegelein F, Guenard D, Lavelle F, Le Goff MT, Mangatal L, Potier P. Relationships between the structure of taxol analogues and their antimitotic activity. J Med Chem. 1991;34:992–998.
- Bissery MC, Guenard D, Gueritte-Voegelein F, Lavelle F. Experimental antitumor activity of taxotere (RP 56976, NSC 628503), a taxol analogue. Cancer Res. 1991;51:4845–4852.
- Mike S, Harrison C, Coles B, Staffurth J, Wilt TJ, Mason MD. Chemotherapy for hormone-refractory prostate cancer. Cochrane Database Syst Rev. CD0052472006
- Quartino AL, Friberg LE, Karlsson MO. A simultaneous analysis of the time-course of leukocytes and neutrophils following docetaxel administration using a semi-mechanistic myelosuppression model. Invest New Drugs. 2010 Dec 14; (E-pub ahead of print)
- Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–422.
- Rozkova D, Tiserova H, Fucikova J, et al. FOCUS on FOCIS: combined chemo-immunotherapy for the treatment of hormone-refractory metastatic prostate cancer. Clin Immunol. 2009;131:1–10.
- Fong L, Kwek SS, O'Brien S, et al. Potentiating endogenous antitumor immunity to prostate cancer through combination immunotherapy with CTLA4 blockade and GM-CSF. Cancer Res. 2009;69:609–615.
- Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–723.
- Small EJ, Tchekmedyian NS, Rini BI, Fong L, Lowy I, Allison JP. A pilot trial of CTLA-4 blockade with human anti-CTLA-4 in patients with hormone-refractory prostate cancer. Clin Cancer Res. 2007;13:1810–1815.
- Bristol-Myers Squibb. ClinicalTrialgov [Internet] Bethesda (MD): National Library of Medicine (US); 2000. Phase 3 Study of Immunotherapy to Treat Advanced Prostate Cancer. [cited 20110824]. Available from: . NCT01057810.
- Bristol-Myers Squibb. ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US); 2000. Study of Immunotherapy to Treat Advanced Prostate Cancer. [cited 20110824]. Available from: . NCT00861614.
- Kobayashi H, Matsunaga K, Oguchi Y. Antimetastatic effects of PSK (Krestin), a protein-bound polysaccharide obtained from basidiomycetes: an overview. Cancer Epidemiol Biomarkers Prev. 1995;4:275–281.
- Lu H, Yang Y, Gad E, et al. Polysaccharide krestin is a novel TLR2 agonist that mediates inhibition of tumor growth via stimulation of CD8 T cells and NK cells. Clin Cancer Res. 2011;17:67–76.
- Mickey DD, Bencuya PS, Foulkes K. Effects of the immunomodulator PSK on growth of human prostate adenocarcinoma in immunodeficient mice. Int J Immunopharmacol. 1989;11:829–838.
- Hayakawa K, Mitsuhashi N, Saito Y, et al. Effect of Krestin as adjuvant treatment following radical radiotherapy in non-small cell lung cancer patients. Cancer Detect Prev. 1997;21:71–77.
- Hayakawa K, Mitsuhashi N, Saito Y, et al. Effect of krestin (PSK) as adjuvant treatment on the prognosis after radical radiotherapy in patients with non-small cell lung cancer. Anticancer Res. 1993;13:1815–1820.
- Iino Y, Yokoe T, Maemura M, et al. Immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer. Anticancer Res. 1995;15:2907–2911.
- Oba K, Teramukai S, Kobayashi M, Matsui T, Kodera Y, Sakamoto J. Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curative resections of gastric cancer. Cancer Immunol Immunother. 2007;56:905–911.
- Nakazato H, Koike A, Saji S, Ogawa N, Sakamoto J. Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Study Group of Immunochemotherapy with PSK for Gastric Cancer. Lancet. 1994;343:1122–1126.
- Sakamoto J, Morita S, Oba K, et al. Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled clinical trials. Cancer Immunol Immunother. 2006;55:404–411.
- Zhang H, Morisaki T, Nakahara C, et al. PSK-mediated NF-kappaB inhibition augments docetaxel-induced apoptosis in human pancreatic cancer cells NOR-P1. Oncogene. 2003;22:2088–2096.
- Kinoshita J, Fushida S, Harada S, et al. PSK enhances the efficacy of docetaxel in human gastric cancer cells through inhibition of nuclear factor-kappaB activation and survivin expression. Int J Oncol. 2010;36:593–600.
- Yamasaki A, Shoda M, Iijima H, et al. A protein-bound polysaccharide, PSK, enhances tumor suppression induced by docetaxel in a gastric cancer xenograft model. Anticancer Res. 2009;29:843–850.
- Vremec D, Shortman K. Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes. J Immunol. 1997;159:565–573.
- Katoh R, Takenoshita S, Shimizu Y, Tanaka S, Yajima Y, Nagamachi Y. Effects on host of modified PVP therapy combined with biological response modifiers in lung cancer. Oncol Rep. 1998;5:103–107.
- Castelo-Branco P, Passer BJ, Buhrman JS, et al. Oncolytic herpes simplex virus armed with xenogeneic homologue of prostatic acid phosphatase enhances antitumor efficacy in prostate cancer. Gene Ther. 2010;17:805–810.
- Dzojic H, Loskog A, Totterman TH, Essand M. Adenovirus-mediated CD40 ligand therapy induces tumor cell apoptosis and systemic immunity in the TRAMP-C2 mouse prostate cancer model. Prostate. 2006;66:831–838.
- Reddy KR, Guan Y, Qin G, Zhou Z, Jing N. Combined treatment targeting HIF-1alpha and Stat3 is a potent strategy for prostate cancer therapy. Prostate. 2011;71:1796–1809.
- Yi H, Yu X, Guo C, Manjili MH, Repasky EA, Wang XY. Adoptive cell therapy of prostate cancer using female mice-derived T cells that react with prostate antigens. Cancer Immunol Immunother. 2011;60:349–360.
- Kato M, Hirose K, Hakozaki M, et al. Induction of gene expression for immunomodulating cytokines in peripheral blood mononuclear cells in response to orally administered PSK, an immunomodulating protein-bound polysaccharide. Cancer Immunol Immunother. 1995;40:152–156.
- Ng TB. A review of research on the protein-bound polysaccharide (polysaccharopeptide, PSP) from the mushroom Coriolus versicolor (Basidiomycetes: Polyporaceae) Gen Pharmacol. 1998;30:1–4.
- Kodama N, Mizuno S, Nanba H, Saito N. Potential antitumor activity of a low-molecular-weight protein fraction from Grifola frondosa through enhancement of cytokine production. J Med Food. 2010;13:20–30.
- Masuda Y, Inoue M, Miyata A, Mizuno S, Nanba H. Maitake beta-glucan enhances therapeutic effect and reduces myelosupression and nephrotoxicity of cisplatin in mice. Int Immunopharmacol. 2009;9:620–626.
- Rubel R, Dalla Santa HS, Bonatto SJ, et al. Medicinal mushroom Ganoderma lucidum (Leyss: Fr) Karst. triggers immunomodulatory effects and reduces nitric oxide synthesis in mice. J Med Food. 2010;13:142–148.
- Si MS, Imagawa DK, Ji P, et al. Immunomodulatory effects of docetaxel on human lymphocytes. Invest New Drugs. 2003;21:281–290.
- Suzuki Y, Tokuda Y. Docetaxel. Gan to Kagaku Ryoho. 2001;28:1363–1367.
- Mason K, Staab A, Hunter N, et al. Enhancement of tumor radioresponse by docetaxel: involvement of immune system. Int J Oncol. 2001;18:599–606.
- Markasz L, Skribek H, Uhlin M, et al. Effect of frequently used chemotherapeutic drugs on cytotoxic activity of human cytotoxic T-lymphocytes. J Immunother. 2008;31:283–293.
- Ogden CL, Fryar CD, Carroll MD, Flegal KM. Mean body weight, height, and body mass index, United States 1960–2002. Adv Data. 2004:1–17.
- Hirono M, Yoshinaka K, Matsuki K, et al. Surgical treatment of Borrmann type 4 (diffuse) gastric cancer. Gan No Rinsho. 1984;30:717–723.
- Kidd PM. The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev. 2000;5:4–27.
Source: PubMed