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


CONCLUSIONS
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.
Department of Surgery, National Hospital Organization Osaka-Minami Medical Center, 2-1 Kidohigashi-cho, Kawachinagano, Osaka 586-8521, Japan.
Koji
K
Tamagawa
Tetsuya
T
Horiuchi
Tsutomu
T
Wada
Kenji
K
Bannai
Takao
T
Ando
D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000503:physiopathology / Q000556:secondary; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011509:Proteoglycans / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000503:physiopathology; D013312:Stress, Physiological / Q000187:drug effects* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D007155:Immunologic Factors; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C010770:polysaccharide-K