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Langenbeck's Archives of Surgery

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01-03-2012 | Original Article

Polysaccharide-K (PSK) may suppress surgical stress-induced metastasis in rat colon cancer

Authors: Koji Tamagawa, Tetsuya Horiuchi, Tsutomu Wada, Kenji Bannai, Takao Ando

Published in: Langenbeck's Archives of Surgery | Issue 3/2012

Abstract

Purpose

We previously demonstrated that hepatic ischemia and reperfusion (I/R) injury increased liver metastasis and cancer growth of RCN-H4 cells. Using a rat model of hepatic I/R-induced liver metastasis, we investigated the metastasis-suppressing effect of polysaccharide-K (PSK), a biological response modifier composed of protein-bound polysaccharide.

Methods

Fischer rats underwent 60 min of 70% partial hepatic ischemia. After 60 min of reperfusion, rat colon adenocarcinoma cells (RCN-H4) were inoculated intrasplenically. PSK was administered orally before I/R, after I/R, or before and after I/R. The weights of metastatic lesions of the liver or the numbers of liver metastatic nodules were determined on day 21. The effect of PSK on angiogenesis was studied by a rat cornea model using RCN-H4 cells or a vascular endothelial growth factor (VEGF)-containing pellet and an in vitro VEGF-induced endothelial cell migration assay.

Results

PSK administration significantly (p < 0.05) suppressed the I/R-induced increase in hepatic metastasis of RCN-H4 cells. The suppression of I/R-promoted metastasis was observed irrespective of the timing of administration. Furthermore, PSK significantly suppressed angiogenesis induced by RCN-H4 cells (p < 0.05) and the VEGF pellet (p < 0.01). PSK significantly suppressed the VEGF-induced migration of vascular endothelial cells (p < 0.05).

Conclusion

PSK may suppress metastasis induced by hepatic I/R. The suppression of angiogenesis by PSK may be one of the mechanisms of the inhibition of hepatic metastasis.

Tamagawa K, Horiuchi T, Uchinami M, Doi K, Yoshida M, Nakamura T, Sasaki H, Taniguchi M, Tanaka K (2008) Hepatic ischemia–reperfusion increases vascular endothelial growth factor and cancer growth in rats. J Surg Res 148:158–163PubMedCrossRef

Doi K, Horiuchi T, Uchinami M, Tabo T, Kimura N, Yokomachi J, Yoshida M, Tanaka K (2002) Hepatic ischemia–reperfusion promotes liver metastasis of colon cancer. J Surg Res 105:243–247PubMedCrossRef

Uchinami M, Muraoka R, Horiuchi T, Tabo T, Kimura N, Tanigawa N (1998) Effect of intermittent hepatic pedicle clamping on free radical generation in the rat liver. Surgery 124:49–56PubMedCrossRef

Nakazato H, Koike A, Saji S, Ogawa N, Sakamoto J (1994) Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Lancet 344:1122–1126CrossRef

Ohwada S, Ikeya T, Yokomori T, Kusaba T, Roppongi T, Takahashi T, Nakamura S, Kakimura S, Iwazaki S, Ishikawa H, Kawate S, Nakajima T, Morishita Y (2004) Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomized controlled study. Br J Cancer 90:1003–1010PubMedCrossRef

Konno K, Motomiya M, Oizumi K, Sato M, Yamamoto F, Tamiya K, Hasuike T, Yokosawa A, Ochiyama T, Ogawa N, Nakai Y (1988) Effect of protein-bound polysaccharide (PSK) in small cell carcinoma of the lung. JJLC 28:19–28CrossRef

Nomoto K, Tsuru S, Awane Y, Kamei H, Ishibiki H, Sekiguchi M, Tamada R, Toge T, Nakajima T (1986) Changes of nonspecific suppressor factors in the serum of gastric cancer patients after surgery and immunochemotherapy. Jpn J Cancer Chemother 13:458–463

Hirose K, Zachariae COC, Oppenheim JJ, Matsushima K (1990) Induction of gene expression and production of immunomodulating cytokines by PSK in human peripheral blood mononuclear cells. Lymphokine Res 9:475–483PubMed

Liu A, Abrise J, Holmgren A, Klein G, Klein E (2005) PSK and Trx80 inhibit B-cell growth in EBV-infected cord blood mononuclear cells through T cells activated by the monocyte products IL-15 and IL-12. Blood 105:1606–1613PubMedCrossRef

10.

Kumar S, Saitoh K, Kumar P (1992) Antiangiogenesis strategies in cancer therapy with special reference to Krestin. In: Steiner R, Weisz PB, Langer R (eds) Angiogenesis: key principles-science-technology-medicine. Birkhauser Werlag, Basel, pp 463–470

11.

Inoue Y, Kashima Y, Aizawa K, Hatakeyama K (1991) A new rat colon cancer cell line metastasizes spontaneously: biologic characteristics and chemotherapeutic response. Jpn J Cancer Res 82:90–97PubMedCrossRef

12.

Volpert OV, Tolsma SS, Pellerin S, Feige J, Chen H, Mosher DF, Bouck M (1995) Inhibition of angiogenesis by thrombospondin-2. Biochem Biophys Res Commun 217:326–332PubMedCrossRef

13.

Karpoff HM, Tung C, Ng B, Fong Y (1996) Interferon gamma protects against hepatic tumor growth in rats by increasing Kupffer cell tumoricidal activity. Hepatology 24:374–379PubMedCrossRef

14.

Oka M, Hazama S, Suzuki M, Wang F, Shimoda K, Iizuka N, Wadamori K, Suzuki T, Attwood S (1994) Depression of cytotoxicity of nonparenchymal cells in the liver after surgery. Surgery 116:877–882PubMed

15.

Ku Y, Kusunoki N, Shiotani M, Maeda I, Iwasaki T, Tominaga M, Kitagawa T, Fukumoto T, Suzuki Y, Kuroda Y (1999) Stimulation of haematogenous liver metastases by ischaemia–reperfusion in rats. Eur J Surg 165:801–807PubMedCrossRef

16.

Suo J, Tanaka N, Hizuka A, Orita K (1994) Suppression of hepatic natural killer activity by liver metastasis of cancer and restoration of killer activity by oral administration of a Basidomycetes-derived polysaccharide, PSK. Acta Medica Okayama 48:237–242PubMed

17.

Matsunaga K, Ohhara M, Oguchi Y, Iijima H, Kobayashi H (1996) Antimetastatic effect of PSK, a protein-bound polysaccharide, against the B16-BL6 mouse melanoma. Invasion Metastasis 16:27–38PubMed

18.

Wada T, Wakamatsu Y, Bannai K, Kato M, Oguchi Y, Matsunaga K, Ando T, Nomoto K (2002) Suppression mechanism of angiogenesis by PSK. Ann Cancer Res Ther 10:93–106

19.

Bao P, Kodra A, Tomic-Canic M, Golinko MS, Ehrlich HP, Brem H (2009) The role of vascular endothelial growth factor in wound healing. J Surg Res 153:347–358PubMedCrossRef

20.

Warzecha Z, Dembinsky A, Ceranowicz P, Dembinsky M, Kownacki P, Konturek SJ, Tomaszewska R, Stachura J, Hladki W, Pawlik WW (2004) Immunohistochemical expression of FGF-2, PDGF-A, VEGF and TGFb RII in the pancreas in the course of ischemia/reperfusion-induced acute pancreatitis. J Physiol Pharmacol 55:791–810PubMed

21.

Werner S, Grose R (2003) Regulation of wound healing by growth factors and cytokines. Physiol Rev 83:835–870PubMed

22.

Yoshida Y, Anand-Apte B, Zetter BR (1996) Differential endothelial migration and proliferation to basic fibroblast growth factor and vascular endothelial growth factor. Growth Factors 113:57–64CrossRef

Title: Polysaccharide-K (PSK) may suppress surgical stress-induced metastasis in rat colon cancer
Authors: Koji Tamagawa
Tetsuya Horiuchi
Tsutomu Wada
Kenji Bannai
Takao Ando
Publication date: 01-03-2012
Publisher: Springer-Verlag
Published in: Langenbeck's Archives of Surgery / Issue 3/2012
Print ISSN: 1435-2443
Electronic ISSN: 1435-2451
DOI: https://doi.org/10.1007/s00423-011-0896-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Polysaccharide-K (PSK) may suppress surgical stress-induced metastasis in rat colon cancer

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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