TY - JOUR AB - Docetaxel, a member of the taxane family, induces antitumor effects in patients with advanced gastric cancer. However, toxicity at therapeutic doses can be severe, resulting in discontinuation of therapy. It is possible that dose reduction due to adverse events may decrease the cytotoxic efficacy of docetaxel. PSK, a protein-bound polysaccharide, has been used as a chemoimmunotherapy agent in the treatment of cancer in Asia for over 30 years. In the present study, we investigated the enhancing effects of PSK on the cytotoxicity of docetaxel in human gastric cancer through non-immunological actions both in vitro and in vivo. The sensitization effects of PSK on docetaxel were evaluated by MTT assay using human gastric cancer cell lines in vitro. In addition, to elucidate the molecular mechanism, we analyzed the activation of NF-κB and the subsequent production of the antiapoptotic molecule survivin in combined treatment with docetaxel and PSK. Accordingly, TMK-1 xenograft growth in SCID mouse was used to evaluate the in vivo efficacy, and the survivin expression in xenografts was also investigated by immunohistochemistry. In vitro, PSK enhanced docetaxel-induced growth inhibition in TMK-1 cells. The docetaxel-induced NF-κB activation was inhibited by adding PSK in a dose-dependent manner. Furthermore, the expression of survivin, which is transcriptionally regulated by NF-κB, was also inhibited by treatment with PSK. In SCID mouse, PSK significantly inhibited growth of TMK-1 subcutaneous xenografts in combination with low-dose docetaxel, and decreased the docetaxel-induced survivin expression in TMK-1 xenografts. Our data suggest that PSK enhanced the efficacy of docetaxel against human gastric cancer both in vitro and in vivo, at least in part, by downregulating NF-κB activation and survivin expression induced by low-dose docetaxel. AD - Gastroenterologic Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan. junkino0416@gmail.co.jp null AU - Kinoshita,Jun AU - Fushida,Sachio AU - Harada,Shinichi AU - Makino,Isamu AU - Nakamura,Keishi AU - Oyama,Katsunobu AU - Fujita,Hideto AU - Ninomiya,Itasu AU - Fujimura,Takashi AU - Kayahara,Masato AU - Ohta,Tetsuo DA - 2010/03/01 DO - 10.3892/ijo_00000534 EP - 600 IS - 3 JO - Int J Oncol PY - 2010 SN - 1019-6439 1791-2423 SP - 593 ST - PSK enhances the efficacy of docetaxel in human gastric cancer cells through inhibition of nuclear factor-κB activation and survivin expression T2 - International Journal of Oncology TI - PSK enhances the efficacy of docetaxel in human gastric cancer cells through inhibition of nuclear factor-κB activation and survivin expression UR - https://doi.org/10.3892/ijo_00000534 VL - 36 ER -