Tumour‐associated macrophage (TAM) is an important component in tumour microenvironment. Generally, TAM exhibits the function of M2‐like macrophage, which was closely related to angiogenesis and tumour progression. Dioscin, a natural steroidal saponin, has shown its powerful anti‐tumour activity recently. However, the mechanism of dioscin involved in immune regulation is still obscure. Here, we observed dioscin induced macrophage M2‐to‐M1 phenotype transition in vitro and inhibited IL‐10 secretion. Meanwhile, the phagocytosis of macrophages was enhanced. In subcutaneous lung tumour models, dioscin inhibited the augmentation of M2 macrophage populations. Furthermore, dioscin down‐regulated STAT3 and JNK signalling pathways in macrophages in vitro. In BMDMs, activating JNK and inhibiting STAT3 induce macrophages to M1 polarization while inhibiting JNK and activating STAT3 to M2 polarization. Additionally, condition mediums from dioscin‐pre‐treated macrophages inhibited the migration of 3LL cells and the tube‐formation capacity of HUVECs. What's more, dioscin‐mediated macrophage polarization inhibited the in vivo metastasis of 3LL cells. In conclusion, dioscin may act as a new anti‐tumour agent by inhibiting TAMs via JNK and STAT3 pathways in lung cancer.

中文翻译：

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薯蓣皂苷通过在肺癌中通过 JNK 和 STAT3 通路抑制巨噬细胞 M2 极化来引发抗肿瘤免疫。

肿瘤相关巨噬细胞（TAM）是肿瘤微环境的重要组成部分。一般来说，TAM表现出M2样巨噬细胞的功能，与血管生成和肿瘤进展密切相关。薯蓣皂苷是一种天然甾体皂苷，最近显示出其强大的抗肿瘤活性。然而，薯蓣素参与免疫调节的机制尚不清楚。在这里，我们在体外观察到薯蓣素诱导巨噬细胞 M2 到 M1 表型转变并抑制 IL-10 分泌。同时，巨噬细胞的吞噬作用增强。在皮下肺肿瘤模型中，薯蓣皂苷抑制 M2 巨噬细胞群的增加。此外，薯蓣皂苷在体外下调巨噬细胞中的 STAT3 和 JNK 信号通路。在 BMDM 中，激活 JNK 和抑制 STAT3 诱导巨噬细胞向 M1 极化，同时抑制 JNK 并激活 STAT3 向 M2 极化。此外，来自薯蓣素预处理的巨噬细胞的条件培养基抑制了 3LL 细胞的迁移和 HUVEC 的管形成能力。此外，薯蓣素介导的巨噬细胞极化抑制了 3LL 细胞的体内转移。总之，薯蓣皂苷可以通过 JNK 和 STAT3 途径抑制肺癌中的 TAM，从而作为一种新的抗肿瘤药物。