Macrophage targeting contributes to the inhibitory effects of embelin on colitis-associated cancer.
Macrophage targeting contributes to the inhibitory effects of embelin on colitis-associated cancer.
复制标题
巨噬细胞靶向有助于 Embelin 对结肠炎相关癌症的抑制作用。
DOI：
10.18632/oncotarget.6969
复制
发表时间：
2016-04-12
期刊：
影响因子：
--
通讯作者：
Qiao L
中科院分区：
文献类型：
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作者：
Wu T;Dai Y;Wang W;Teng G;Jiao H;Shuai X;Zhang R;Zhao P;Qiao L
巨噬细胞是炎症和肿瘤微环境的主要组成部分。我们以前报道过恩贝林抑制结肠炎相关的肿瘤发生。在此，研究了Embelin的抗炎和抗肿瘤特性中的巨噬细胞靶向作用。通过使用结肠炎相关癌症（CAC）模型，我们证明了恩贝林通过阻断结肠巨噬细胞的募集而显著地消耗结肠巨噬细胞。此外，Embelin减弱了肿瘤微环境中巨噬细胞的M2样极化，并消除了其在CAC发展过程中的促肿瘤功能。Embelin有效抑制巨噬细胞中的NF-κB信号传导，并减少CAC中涉及的关键促炎细胞因子和致瘤因子（如TNFα、IL-6和考克斯-2）的产生。此外，即使在Th 2细胞因子的存在下，Embelin也直接降低了体外M2巨噬细胞的极化。这些结果表明，靶向巨噬细胞是，至少部分地，负责CAC中的Embelin的抗肿瘤活性。我们的观察加强了未来验证恩贝林预防和治疗CAC的理论基础
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