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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

五甲基槲皮素通过IFN-γ信号传导抑制肝癌进展和脂肪细胞诱导的PD-L1表达。

卷 20, 期 11, 2020

页: [868 - 874] 页: 7

弟呕挨: 10.2174/1568009620999200730184514

价格: $65

摘要

背景：肥胖是癌症类型发展的重要危险因素。程序性死亡1及其配体程序性死亡配体1（PD-L1）在肿瘤免疫逃逸中起关键作用。虽然，PD-L1在肥胖相关性肝细胞癌（HCC）中的作用仍然未知。我们先前显示天然黄酮类五甲基槲皮素（PMQ）具有抗肥胖特性。 目的：本研究旨在研究PMQ对肥胖小鼠肝癌发展的影响，以及PMQ是否调节PD-L1及其在肝癌中的表达。 方法：用谷氨酸钠诱导的肥胖小鼠接种H22肿瘤细胞。测量肿瘤体积和重量。在体外，分化3T3-L1前脂肪细胞并通过油红色染色测量脂质蓄积，并通过Elisa检测IFN-γ水平。肝癌HepG2细胞用3T3-L1脂肪细胞（adi-CM）的条件培养基处理。免疫印迹用于检测肿瘤组织和HepG2细胞中PD-L1蛋白的水平。 结果：与对照组小鼠相比，肥胖小鼠的H22肿瘤生长更快且PD-L1蛋白水平更高。 PMQ抑制H22肿瘤的生长并降低肿瘤组织中PD-L1的表达。在adi-CM处理的HepG2细胞中，PD-L1蛋白水平升高。在adi-CM中可检测到IFN-γ，外源IFN-γ诱导HepG2细胞中PD-L1表达。 PMQ影响3T3-L1前脂肪细胞的分化，降低脂肪细胞分泌的IFN-γ水平，并下调adi-CM诱导的HepG2细胞中PD-L1表达。结论：PMQ至少可以部分通过抑制IFN-γ信号下调脂肪细胞诱导的PD-L1表达来抑制肥胖小鼠的HCC进展。

关键词: 五甲基槲皮素，脂肪细胞，H22，HepG2，PD-L1，IFN-γ。

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