Flavonoid Group of Smilax glabra Roxb. Regulates the Anti-Tumor Immune Response Through the STAT3/HIF-1 Signaling Pathway.
Flavonoid Group of Smilax glabra Roxb. Regulates the Anti-Tumor Immune Response Through the STAT3/HIF-1 Signaling Pathway.
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土茯苓黄酮类化合物。
DOI：
10.3389/fphar.2022.918975
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发表时间：
2022
影响因子：
5.6
通讯作者：
Fu, Huiying
中科院分区：
文献类型：
--
作者：
Guo, Yingxue;Mao, Weiye;Jin, Lu;Xia, Linying;Huang, Jie;Liu, Xia;Ni, Ping;Shou, Qiyang;Fu, Huiying
关键词：
背景：光肩星天牛。SGR是一种应用广泛的中药，具有增强免疫力的作用。然而，其抗肿瘤作用及其作用机制尚不清楚。方法：选用MMTV-PYMT小鼠，测定SGR乙酸乙酯(SGR-EA)的抗肿瘤作用。首先，用流式细胞术检测小鼠肿瘤微环境中免疫细胞的数量。体外刺激巨噬细胞M2极化，检测巨噬细胞M1/M2表面标志和mRNA的表达。最后，我们对SGR-EA的活性成分进行了网络药理学分析和体外实验，以验证SGR-EA通过将M2巨噬细胞重置为M1表型来调控缺氧诱导因子-1信号通路，从而调节抗肿瘤免疫反应，从而抑制小鼠肿瘤生长和肺转移。结果：SGR-EA对小鼠肿瘤生长和肺转移均有抑制作用。肿瘤相关巨噬细胞从M2表型转变为肿瘤杀伤M1表型，并促进肿瘤微环境中CD4+和CD8+T细胞的募集。在体外，SGR-EA显著抑制巨噬细胞向M2巨噬细胞的极化，增加M1巨噬细胞的数目。此外，经SGR-EA干预后，IL-4刺激的巨噬细胞HIF-1信号通路相关蛋白的表达明显受到抑制。结论：SGR-EA通过抑制HIF-1信号通路的激活而发挥抗肿瘤作用，并通过使肿瘤相关巨噬细胞向M1表型转化而发挥抗肿瘤作用。
Background: Smilax glabra Roxb. (SGR) is a widely used traditional Chinese medicine, which has known effects of enhancing immunity. However, its anti-tumor effects and mechanism of action are still unclear. Methods: We selected MMTV-PyMT mice to determine the anti-tumor efficacy of SGR ethyl acetate (SGR-EA). First, flow cytometry was used to detect the number of immune cells in the mice tumor microenvironment. Furthermore, M2 polarization of macrophages was stimulated in vitro, and the expressions of macrophage M1/M2 surface markers and mRNA were as determined. Finally, we carried out a network pharmacology analysis on the active components of SGR-EA and in vitro experiments to verify that SGR-EA regulated the hypoxia-inducible factor (HIF)-1 signaling pathway to modulate the anti-tumor immune response by resetting M2 macrophages toward the M1 phenotype which inhibited tumor growth and lung metastasis in the mice. Result: SGR-EA inhibited tumor growth and lung metastasis in the mice. Tumor-associated macrophages switched from M2 to the tumor-killing M1 phenotype and promoted the recruitment of CD4+ and CD8+ T cells in the tumor microenvironment. In vitro, SGR-EA significantly inhibited the polarization of macrophages into M2 macrophages and increased the number of M1 macrophages. In addition, following an intervention with SGR-EA, the expression of the HIF-1 signaling pathway-related proteins stimulated by interleukin-4 in macrophages was significantly inhibited. Conclusion: SGR-EA played an anti-tumor role by inhibiting the activation of the HIF-1 signaling pathway and response by resetting tumor-associated macrophages toward the M1 phenotype.
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影响因子：
5.3
作者：
Xu Q;Liu Z;Cao Z;Shi Y;Yang N;Cao G;Zhang C;Sun R;Zhang C
通讯作者：
Zhang C
DOI：
10.1038/nrclinonc.2016.217
发表时间：
2017-07
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Mantovani A;Marchesi F;Malesci A;Laghi L;Allavena P
通讯作者：
Allavena P
影响因子：
64.5
作者：
Binnewies, Mikhail;Mujal, Adriana M.;Krummel, Matthew F.
通讯作者：
Krummel, Matthew F.
影响因子：
5.6
作者：
Chao, Yufan;Gao, Songyan;Dong, Xin
通讯作者：
Dong, Xin
中华被毛真菌通过 T-bet/Eomes 参与肿瘤微环境调节 CD8 T 细胞耗竭
影响因子：
5.6
作者：
Jin L;Jin L;Wu R;Liu X;Zhu X;Shou Q;Fu H
通讯作者：
Fu H