A Protein-bound Polysaccharide, PSK, Enhances Tumor Suppression Induced by Docetaxel in a Gastric Cancer Xenograft Model

Background: We have reported previously that docetaxel (TXT) induces apoptosis and nuclear factor-kappaB (NF- K B) activation, and that blockade of NF-K B activation augments TXT-induced apoptosis in human gastric cancer cells. In addition, we have also shown that a protein-bound polysaccharide PSK enhances TXT-induced apoptosis through NF-κB inhibition in human pancreatic cancer cells. Based on these observations, in the present study the possibility that PSK could enhance TXT-mediated tumor suppression was examined in vivo and in vitro. Materials and Methods: A gastric cancer xenograft model was used to examine the enhanced TXT-mediated tumor suppression by PSK in vivo. The effects of PSK on proliferation and apoptosis induced by TXT in gastric cancer cells were evaluated in vitro using a human gastric cancer cell line, MK-1. The effect of PSK on increased TXT-induced invasion was also measured. Results: PSK enhanced TXT-mediated tumor suppression in vivo. Immunohistochemical analyses of the tumors revealed that TXT increased NF- K B activation in the tumors and this was suppressed by PSK. In the ex vivo experimental system, PSK enhanced the growth inhibition and apoptosis induced by TXT in the MK- cells and reduced the increased invasive ability induced by TXT. Conclusion: PSK enhanced TXT-induced tumor suppression in a gastric cancer xenograft model.