Abstract 4421: Curucmin suppresses myeloid-derived suppressor cells and inhibits gastric cancer growth

Abstract

Abstract Myeloid-derived suppressor cells (MDSCs) are accumulated in the spleen and tumor and contribute to tumor growth, angiogenesis and progression. In this study, we examined the effects of curcumin, a compound from turmeric, on MDSCs and gastric cancer growth in vivo. BABL/C nude mice injected subcutaneously with gastric cancer MKN-45 cells were fed with control diet or 2% curcumin diet or received curucmin through daily i.p. injection at 50mg/kg body weight. Cell apoptosis were determined by Flow cytometer and TUNEL staining. Protein expressions were determined by Western Blot and Immunohistochemistry staining. The frequencies of myeloid-derived suppress cells in the mice were analyzed by Flow cytometer. Cytokines were determined by ELISA. Tumors growth was significantly inhibited by both 2% curucumin diet and curcumin i.p. injection treatment. The frequencies of MDSCs in the spleen, blood and tumor tissues were significantly decreased in the tumor-bearing mice after a 5-days or a 4-weeks treatment with curcumin (in diet or by i.p. injection) compared to control treatment. MDSCs isolated from the spleen of curcumin-treated mice secreted lower levels of IL-6, compared to that from untreated mice. The treatment of MDSCs isolated from the spleen of the untreated tumor-bearing mice with curcumin had lower levels of IL-6, compared to that of control mice. Furthermore, curcumin treatment significantly reduced IL-6 level secreted by IL-1beta-induced MDSCs. Curucmin treatment also significantly induced apoptosis of gastric cancer cells in vitro and in vivo. Our results demonstrate for the first time that cucumin could inhibit MDSCs mobilization and activation and that curcumin inhibits gastric cancer partly through suppressing MDSCs mobilization and activation. MDSCs may be a new target of cucumin for gastric cancer therapy and prevention. (The project was supported by NIH grant R21CA149865 (Tu SP)). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4421. doi:10.1158/1538-7445.AM2011-4421