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.
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, ratcolon 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.
Authors: O V Volpert; S S Tolsma; S Pellerin; J J Feige; H Chen; D F Mosher; N Bouck Journal: Biochem Biophys Res Commun Date: 1995-12-05 Impact factor: 3.575
Authors: S Ohwada; T Ikeya; T Yokomori; T Kusaba; T Roppongi; T Takahashi; S Nakamura; S Kakinuma; S Iwazaki; H Ishikawa; S Kawate; T Nakajima; Y Morishita Journal: Br J Cancer Date: 2004-03-08 Impact factor: 7.640