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

• Published in: Anticancer research 2009-03, Vol.29 (3), p.843-850
• Main Authors: YAMASAKI, Akio, SHODA, Momoko, IKEBE, Mio, JO, E. I, SATO, Norihiro, NAKAMURA, Masafumi, SEKINE, Fujio, MORISAKI, Takashi, KATANO, Mitsuo, IIJIMA, Hiroko, NAGAI, Shuntaro, WADA, Junji, SUZUKI, Hiroyuki, CHIKAZAWA, Nobuhito, TASAKA, Takehiko, KAMEDA, Chizu, TANAKA, Haruo
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - secondary; Animals; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; Biological and medical sciences; Cell Movement - drug effects; Cell Proliferation - drug effects; Chemotherapy; Drug Synergism; Electrophoretic Mobility Shift Assay; Female; Humans; Immunoenzyme Techniques; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; NF-kappa B - genetics; NF-kappa B - metabolism; Pharmacology. Drug treatments; Proteoglycans - administration & dosage; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Survival Rate; Taxoids - administration & dosage; Tumor Cells, Cultured; Tumors; Xenograft Model Antitumor Assays
• ISSN: 0250-7005; 1791-7530

Background: We have reported previously that docetaxel (TXT) induces apoptosis and nuclear factor-kappaB (NF-κB) activation, and that blockade of NF-κB 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-κB 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-1 cells and reduced the increased invasive ability induced by TXT. Conclusion: PSK enhanced TXT-induced tumor suppression in a gastric cancer xenograft model.