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8-溴-7-甲氧基白杨素逆转肝癌干细胞样细胞诱导的肿瘤相关巨噬细胞的M2极化

8-bromo-7-methoxychrysin Reversed M2 Polarization of Tumor-associated Macrophages Induced by Liver Cancer Stem-like Cells.

作者信息

Sun Shuwen, Cui Yinghong, Ren Kaiqun, Quan Meifang, Song Zhenwei, Zou Hui, Li Duo, Zheng Yu, Cao Jianguo

机构信息

Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha, 410013,China.

出版信息

Anticancer Agents Med Chem. 2017;17(2):286-293. doi: 10.2174/1871520616666160204112556.

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is related to chronic liver inflammation. M2 polarization of tumor-associated macrophages (TAMs) in the tumor microenvironment promotes liver cancer stem-like cell (LCSLC) self-renewal capability and carcinogenicity. Therefore, reversing M2 polarization of TAMs could be an effective approach to cure HCC.

OBJECTIVE

To evaluate whether 8-bromo-7-methoxychrysin (BrMC) has an effect on M2 polarization of TAMs.

METHOD

LCSLC and conditional medium were obtained by sphere forming assay. Identification of LCSLC were analyzed by sphere forming, wound-healing and invasion assay. TAM and effects of BrMC on it were validated by immunofluorescence staining, ELISA and griess assay. Expressions of cancer stem cell and macrophage marker were analyzed by western blotting.

RESULTS

Our results showed that BrMC significantly suppressed the expression of the M2 macrophage marker CD163. Furthermore, BrMC influenced the secretion profile of cytokines of TAMs. Mechanistically, BrMC reversed M2 polarization of TAMs due to inhibition of NF-κB activation.

CONCLUSION

BrMC may be a potentially novel flavonoid agent that can be applied for disrupting the interaction of LCSLCs and TAMs.

摘要

背景

肝细胞癌(HCC)与慢性肝脏炎症相关。肿瘤微环境中肿瘤相关巨噬细胞(TAM)的M2极化促进肝癌干细胞样细胞(LCSLC)的自我更新能力和致癌性。因此,逆转TAM的M2极化可能是治愈HCC的有效方法。

目的

评估8-溴-7-甲氧基白杨素(BrMC)对TAM的M2极化是否有影响。

方法

通过成球试验获得LCSLC和条件培养基。通过成球、伤口愈合和侵袭试验分析LCSLC的鉴定。通过免疫荧光染色、ELISA和格里斯试验验证TAM及其对BrMC的影响。通过蛋白质印迹分析癌症干细胞和巨噬细胞标志物的表达。

结果

我们的结果表明,BrMC显著抑制M2巨噬细胞标志物CD163的表达。此外,BrMC影响TAM的细胞因子分泌谱。机制上,BrMC通过抑制NF-κB激活逆转TAM的M2极化。

结论

BrMC可能是一种潜在的新型黄酮类药物,可用于破坏LCSLC与TAM之间的相互作用。

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