研究动态
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柴胡-白芍通过激活免疫微环境中的 PTEN/PD-L1 轴来抑制肝细胞癌的发展。

Radix Bupleuri-Radix Paeoniae Alba Inhibits the Development of Hepatocellular Carcinoma through Activation of the PTEN/PD-L1 Axis within the Immune Microenvironment.

发表日期:2023 Nov 01
作者: Fan Zhang, Kun Zhou, Wei Yuan, Kewei Sun
来源: PHARMACOLOGY & THERAPEUTICS

摘要:

本研究探讨了柴胡-白芍 (BP) 对肝细胞癌 (HCC) 的活性。利用中药系统药理学 (TCMSP) 数据库确定了 BP 的活性成分和抗 HCC 的潜在靶点。分子对接分析验证了PTEN与BP成分的结合活性。 H22细胞用于在雄性balb/c小鼠中建立HCC模型。采用免疫荧光染色、免疫组织化学、流式细胞术、蛋白质印迹、酶联免疫吸附测定和实时定量PCR来研究雄性balb/c小鼠增殖、凋亡、PTEN水平、炎症和T细胞分化的变化。 BP 中的主要活性成分是槲皮素、山奈酚、异鼠李素、豆甾醇和 β-谷甾醇。分子对接表明这五种BP活性成分与PTEN形成了稳定的复合物。 BP 在我们的 HCC 小鼠模型中表现出抗肿瘤作用。研究发现 BP 可以增加 HCC 小鼠的 CD8 和 IFN-γ /CD4 T 细胞水平,同时降低 PD-1 /CD8 T 和 Treg 细胞水平。 BP 上调 HCC 小鼠的 IL-6、IFN-γ 和 TNF-α 水平,但下调 IL-10 水平。 PTEN 敲低后,BP 诱导的效应被消除。BP 通过激活 PTEN/PD-L1 轴影响免疫微环境,从而预防 HCC。
This study investigated how Radix Bupleuri-Radix Paeoniae Alba (BP) was active against hepatocellular carcinoma (HCC).Traditional Chinese medicine systems pharmacology (TCMSP) database was employed to determine the active ingredients of BP and potential targets against HCC. Molecular docking analysis verified the binding activity of PTEN with BP ingredients. H22 cells were used to establish an HCC model in male balb/c mice. Immunofluorescence staining, immunohistochemistry, flow cytometry, western blotting, enzyme-linked immunosorbent assay, and real-time quantitative PCR were used to study changes in proliferation, apoptosis, PTEN levels, inflammation, and T-cell differentiation in male balb/c mice.The major active ingredients in BP were found to be quercetin, kaempferol, isorhamnetin, stigmasterol, and beta-sitosterol. Molecular docking demonstrated that these five active BP ingredients formed a stable complex with PTEN. BP exhibited an anti-tumor effect in our HCC mouse model. BP was found to increase the CD8+ and IFN-γ+/CD4+ T cell levels while decreasing the PD-1+/CD8+ T and Treg cell levels in HCC mice. BP up-regulated the IL-6, IFN-γ, and TNF-α levels but down-regulated the IL-10 levels in HCC mice. After PTEN knockdown, BP-induced effects were abrogated.BP influenced the immune microenvironment through activation of the PTEN/PD-L1 axis, protecting against HCC.