Luteolin inhibits recruitment of monocytes and migration of Lewis lung carcinoma cells by suppressing chemokine (C-C motif) ligand 2 expression in tumor-associated macrophage
Luteolin inhibits recruitment of monocytes and migration of Lewis lung carcinoma cells by suppressing chemokine (C-C motif) ligand 2 expression in tumor-associated macrophage
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DOI：
10.1016/j.bbrc.2016.01.002
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发表时间：
2016-01-29
影响因子：
3.1
通讯作者：
Ha, Ki-Tae
中科院分区：
文献类型：
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作者：
Choi, Hee-Jin;Choi, Hee-Jung;Ha, Ki-Tae
肿瘤相关巨噬细胞（TAM）在癌症的进展中起着关键作用。为了研究抑制TAM的肿瘤支持M2样表型的新候选物，用白细胞介素（IL）-4处理鼠巨噬细胞系RAW 264.7细胞。木犀草素可抑制IL-4下游信号转导子和转录激活子6（STAT 6）的磷酸化，并降低M2相关基因的表达。此外，分泌的细胞因子的Luminex多重分析显示，IL-4增强的趋化因子（C-C基序）配体2（CCL 2）的分泌被毛地黄黄酮处理减少。IL-4刺激的单核细胞，THP-1细胞的迁移，抑制了毛地黄黄酮治疗和重组CCL 2补充恢复。此外，木犀草素以CCL 2依赖的方式减少刘易斯肺癌细胞的迁移。鉴于TAM表型在肿瘤微环境中的重要作用，毛地黄黄酮通过抑制TAM分泌的CCL 2对单核细胞募集和癌症迁移的抑制作用可能提示治疗恶性肿瘤的新治疗方法。(C)2016 Elsevier Inc. All rights reserved.
Tumor-associated macrophages (TAMs) play pivotal roles in the progression of cancer. In order to investigate a novel candidate that inhibits the tumor-supporting M2-like phenotype of TAMs, a murine macrophage cell line RAW 264.7 cells were treated with interleukin (IL)-4. Luteolin inhibited phosphorylation of signal transducer and activator of transcription 6 (STAT6), a main downstream signal of IL-4, and reduced the expression of the M2-associated genes. In addition, Luminex multiplex analysis for secreted cytokines revealed that IL-4-enhanced secretion of chemokine (C-C motif) ligand 2 (CCL2) was reduced by luteolin treatment. IL-4-stimulated migration of monocyte, THP-1 cells, was inhibited by luteolin treatment and recovered by recombinant CCL2 supplement. Moreover, luteolin decreased migration of Lewis lung carcinoma cells in a CCL2-dependent manner. Given the important role of the TAM phenotype in the tumor microenvironment, inhibitory effect of luteolin on the monocyte recruitment and cancer migration via suppression of the TAM-secreted CCL2 may suggest a novel therapeutic approach to treat malignant tumors. (C) 2016 Elsevier Inc. All rights reserved.