Macrophage targeting contributes to the inhibitory effects of embelin on colitis-associated cancer
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Ting Wu1, Yun Dai1, Weihong Wang1, Guigen Teng1, Hongmei Jiao2, Xiaowei Shuai1, Rongxin Zhang3, Peng Zhao4, Liang Qiao5
1Department of Gastroenterology, Peking University First Hospital, Beijing 100034, China
2Department of Gerontology, Peking University First Hospital, Beijing 100034, China
3Research Center of Basic Medical Sciences and Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China
4Department of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
5Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, NSW 2145, Australia
Yun Dai, e-mail: [email protected]
Liang Qiao, e-mail: [email protected]
Keywords: embelin, colitis-associated cancer, macrophage, target therapy
Received: September 04, 2015 Accepted: January 06, 2016 Published: January 21, 2016
Macrophages are a major component of inflammatory and tumor microenvironment. We previously reported that embelin suppresses colitis-associated tumorigenesis. Here, the role of macrophage targeting in the anti-inflammatory and anti-tumor properties of embelin was investigated. By using colitis-associated cancer (CAC) model, we demonstrated that embelin significantly depleted colon macrophages by blocking their recruitment. Moreover, embelin attenuated M2-like polarization of macrophages within the tumor microenvironment and eliminated their tumor-promoting functions during the development of CAC. Embelin potently inhibited NF-κB signaling in macrophages and decreased the production of key pro-inflammatory cytokines and tumorigenic factors involved in CAC, such as TNFα, IL-6 and COX-2. In addition, embelin directly reduced the polarization of M2 macrophages in vitro even in the presence of Th2 cytokines. These results suggested that targeting macrophages is, at least in part, responsible for the anti-tumor activity of embelin in CAC. Our observations strengthen the rationale for future validation of embelin in the prevention and treatment of CAC
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