抑肺饮调控巨噬细胞表型干预肺癌转移的作用研究  

Effects of Yifei Yin on inhibiting lung cancer metastasis by regulating macrophage phenotype

作　　者：汪一帆[1] 应栩华[1] 陈观平[1] 李明乾[1] 柴可群[1] WANG Yi-fan;YING Xu-hua;CHEN Guan-ping;LI Ming-qian;CHAI Ke-qun(Cancer Institute of Integrative Medicine,Tongde Hospital of Zhejiang Province(Zhejiang Academy of Traditional Chinese Medicine),Hangzhou 310012,China)

机构地区：[1]浙江省立同德医院(浙江省中医药研究院)中西医结合肿瘤研究所,杭州310012

出　　处：《中华中医药杂志》2022年第3期1389-1394,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：浙江省中医药科技计划项目(No.2021ZB073,No.2019ZB028);浙江省基础公益研究计划项目(No.LGF22H280015,No.LGF18H290003);国家自然科学基金项目(No.81673809)。

摘　　要：目的:从TLR2信号通路着手,探讨抑肺饮调控巨噬细胞表型干预肺癌转移的作用机制。方法:利用肺癌细胞和巨噬细胞共培养体系,探讨抑肺饮对巨噬细胞表型以及对肺癌细胞生长、侵袭和迁移功能的影响;荧光定量PCR检测抑肺饮对肺癌细胞中TLR2信号通路相关分子mRNA表达水平的影响。通过小鼠肺癌移植瘤模型,考察抑肺饮对肺癌生长、转移以及肿瘤相关巨噬细胞(TAMs)浸润的干预作用。结果:在肺癌细胞与巨噬细胞共培养的条件下,抑肺饮作用后M2型巨噬细胞的比例下降,M1型巨噬细胞的比例上升;与空白血清对照组比较,抑肺饮含药血清组M2型巨噬细胞标志物Arg1和CD206的表达水平显著下调(P<0.01),M1型巨噬细胞标志物iNOS和CD86的表达水平显著上调(P<0.05),肺癌细胞的生长、侵袭和迁移能力受到抑制(P<0.01,P<0.05),TLR2、CCL2和CCL5 mRNA表达水平显著下调(P<0.05,P<0.01)。在体内水平,抑肺饮具有抗肿瘤生长和转移的作用,其中顺铂+抑肺饮组的抑瘤率最高,抑制转移效果最佳;与模型组比较,抑肺饮高剂量组肿瘤组织中CD163的表达水平下调。结论:抑肺饮可能通过抑制TLR2信号通路,调节巨噬细胞表型,重塑肿瘤免疫微环境发挥干预肺癌生长和转移的作用。Objective: To understand the mechanism of Yifei Yin in inhibiting lung cancer metastasis by regulating macrophage phenotype based on TLR2 signaling pathway. Methods: To investigate the effect of Yifei Yin on tumor-associated macrophages(TAMs) phenotype, as well as the impact on the proliferation, invasion and migration of lung cancer cells by using lung cancer cells and macrophages co-culture system;to delineate the effect of Yifei Yin on the mRNA expression levels of TLR2and related inflammatory factors in lung cancer cells by performing qRT-PCR;to explore the effects of Yifei Yin on growth and metastasis of lung cancer and the infiltration of TAMs in vivo through lung cancer mice of subcutaneous tumor transplantation.Results: Under the co-culture condition, the proportion of M2 macrophages was decreased, while the proportion of M1 macrophages was increased after treating with Yifei Yin. Yifei Yin can inhibited the expression levels of Arg1 and CD206 in macrophages(P<0.01), and increased the expression levels of iNOS and CD86(P<0.05). In addition, Yifei Yin can suppress the proliferation,invasion and migration of lung cancer cells, and downregulate the mRNA expression levels of TLR2, CCL2 and CCL5(P<0.05,P<0.01). In vivo study showed that Yifei Yin could inhibit the growth and metastasis of lung cancer cells. The most obvious inhibitory effect was observed in the Yifei Yin combined with DDP group. Compared with the model group, the expression level of CD163 was decreased in the Yifei Yin high dosage group. Conclusion: Yifei Yin may regulate the phenotype of macrophages through TLR2 signaling pathway, and inhibit the growth and metastasis of lung cancer by remodeling tumor immune microenvironment.

关 键 词：抑肺饮 肺癌 转移 肿瘤相关巨噬细胞 肿瘤微环境 

分 类 号：R285[医药卫生—中药学]