Wu Ting, Dai Yun, Wang Weihong, Teng Guigen, Jiao Hongmei, Shuai Xiaowei, Zhang Rongxin, Zhao Peng, Qiao Liang
Department of Gastroenterology, Peking University First Hospital, Beijing 100034, China.
Department of Gerontology, Peking University First Hospital, Beijing 100034, China.
Oncotarget. 2016 Apr 12;7(15):19548-58. doi: 10.18632/oncotarget.6969.
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.
巨噬细胞是炎症和肿瘤微环境的主要组成部分。我们之前报道过 embelin 可抑制结肠炎相关的肿瘤发生。在此，研究了靶向巨噬细胞在 embelin 的抗炎和抗肿瘤特性中的作用。通过使用结肠炎相关癌症（CAC）模型，我们证明 embelin 通过阻断结肠巨噬细胞的募集使其显著减少。此外，embelin 减弱了肿瘤微环境中巨噬细胞的 M2 样极化，并在 CAC 发展过程中消除了它们的促肿瘤功能。Embelin 有力地抑制了巨噬细胞中的 NF-κB 信号传导，并减少了参与 CAC 的关键促炎细胞因子和致瘤因子的产生，如 TNFα、IL-6 和 COX-2。此外，即使在存在 Th2 细胞因子的情况下，embelin 在体外也能直接降低 M2 巨噬细胞的极化。这些结果表明，靶向巨噬细胞至少部分地促成了 embelin 在 CAC 中的抗肿瘤活性。我们的观察结果为未来验证 embelin 在预防和治疗 CAC 方面提供了理论依据。
