Resveratrol Prevents Tumor Growth and Metastasis by Inhibiting Lymphangiogenesis and M2 Macrophage Activation and Differentiation in Tumor-ssociated Macrophages
Resveratrol Prevents Tumor Growth and Metastasis by Inhibiting Lymphangiogenesis and M2 Macrophage Activation and Differentiation in Tumor-ssociated Macrophages
复制标题
DOI：
10.1080/01635581.2016.1158295
复制
发表时间：
2016-01-01
影响因子：
2.9
通讯作者：
Sumiyoshi, Maho
中科院分区：
文献类型：
--
作者：
Kimura, Yoshiyuki;Sumiyoshi, Maho
白藜芦醇通过调节肿瘤相关巨噬细胞中的M2巨噬细胞对肿瘤诱导的淋巴管生成的抗肿瘤和抗转移作用目前尚不清楚。因此，我们在此研究了白藜芦醇对M2巨噬细胞活化和分化的影响，以及白藜芦醇处理的条件培养基（CM）在M2巨噬细胞中对血管内皮细胞生长因子（VEGF）-C诱导的迁移，侵袭和人淋巴管内皮细胞（HLEC）管形成的影响。白藜芦醇（50 μ M或5-50 μ M）抑制M2巨噬细胞中白细胞介素-10和单核细胞趋化蛋白-1的产生，而它促进转化生长因子-β（1）的产生。白藜芦醇（25和50 μ M）抑制信号转导和转录激活因子3的磷酸化，而不影响其在M2巨噬细胞分化过程中的表达。此外，白藜芦醇处理的CM的M2巨噬细胞抑制VEGF-C诱导的HLEC迁移，侵袭和淋巴管生成。白藜芦醇（25毫克/公斤，每天两次）抑制肿瘤生长和转移到肺，也减少了淋巴管内皮细胞在肿瘤（体内）的面积。这些结果表明，白藜芦醇的抗肿瘤和抗转移作用部分是通过调节M2巨噬细胞的活化和分化而抑制淋巴管生成。
Antitumor and antimetastatic effects of resveratrol on tumor-induced lymphangiogenesis through the regulation of M2 macrophages in tumor-associated macrophages currently remain unknown. Therefore, we herein examined the effects of resveratrol on M2 macrophage activation and differentiation, and those of resveratrol-treated condition medium (CM) in M2 macrophages on vascular endothelial cell growth factor (VEGF)-C-induced migration, invasion, and tube formation by human lymphatic endothelial cells (HLECs). Resveratrol (50 mu M or 5-50 mu M) inhibited the production of interleukin-10 and monocyte chemoattractant protein-1 in M2 macrophages, whereas it promoted that of transforming growth factor-beta(1). Resveratrol (25 and 50 mu M) inhibited the phosphorylation of signal transducer and activator of transcript 3 without affecting its expression in the differentiation process of M2 macrophages. Furthermore, resveratrol-treated CM of M2 macrophages inhibited VEGF-C-induced HLEC migration, invasion, and lymphangiogenesis. Resveratrol (25 mg/kg, twice daily) inhibited tumor growth and metastasis to the lung and also reduced the area of lymphatic endothelial cells in tumors (in vivo). These results suggest that the antitumor and antimetastatic effects of resveratrol were partly due to antilymphangiogenesis through the regulation of M2 macrophage activation and differentiation.