Background

The flavonoid galangin (3,5,7-trihydroxyflavone) is derived from the root of Alpinia officinarum Hance, an edible and medicinal herb. Galangin has many biological activities, such as anti-inflammatory, anti-microbial, anti-viral, anti-obesogenic, and anti-oxidant effects. However, the anti-tumor mechanism of galangin remains unclear.

Purpose

To elucidate the anti-tumor mechanisms of galangin in vitro and in vivo.

Methods

MTT, western blotting, immunoprecipitation, RT-PCR, and immunofluorescence assays were used to assess the mechanism of galangin inhibiting PD-L1 expression. The effect of galangin on T cell activity was analyzed in Hep3B/T cell co-cultures. Colony formation, EdU, migration, and invasion assays were performed to explore the effect of galangin on cancer progression and metastasis. Anti-tumor effects of galangin were investigated in a xenograft model.

Results

Galangin inhibited PD-L1 expression dose-dependently, which plays a major role in tumor progression. Moreover, galangin blocked STAT3 activation through the JAK1/JAK2/Src signaling pathway and Myc activation through the Ras/RAF/MEK/ERK signaling pathway. Galangin reduced PD-L1 expression by suppressing STAT3 and Myc cooperatively. Galangin increased the killing effect of T cells on tumor cells in Hep3B/T cell co-cultures. Moreover, galangin inhibited tumor cell proliferation, migration, and invasion through PD-L1. In vivo experiments showed that galangin suppressed tumor growth.

Conclusion

Galangin enhances T-cell activity and inhibits tumor cell proliferation, migration, and invasion through PD-L1. The current study emphasizes the anti-tumor properties of galangin, offering new insights into the development of tumor therapeutics targeting PD-L1.

中文翻译：

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高良姜素通过抑制 STAT3 和 MYC 抑制程序性细胞死亡配体 1 表达并增强 T 细胞肿瘤杀伤活性

背景

类黄酮高良姜素（3,5,7-三羟基黄酮）来源于可食用和可药用的植物良姜的根部。高良姜素具有抗炎、抗微生物、抗病毒、抗致肥胖、抗氧化等多种生物活性。然而，高良姜素的抗肿瘤机制仍不清楚。

目的

阐明高良姜素的体外和体内抗肿瘤机制。

方法

MTT、蛋白质印迹、免疫沉淀、RT-PCR 和免疫荧光分析用于评估高良姜素抑制 PD-L1 表达的机制。在 Hep3B/T 细胞共培养物中分析了高良姜素对 T 细胞活性的影响。进行集落形成、EdU、迁移和侵袭测定以探索高良姜素对癌症进展和转移的影响。在异种移植模型中研究了高良姜素的抗肿瘤作用。

结果

高良姜素剂量依赖性地抑制 PD-L1 表达，这在肿瘤进展中起着重要作用。此外，高良姜素通过 JAK1/JAK2/Src 信号通路阻断 STAT3 激活，通过 Ras/RAF/MEK/ERK 信号通路阻断 Myc 激活。高良姜素通过协同抑制 STAT3 和 Myc 来降低 PD-L1 的表达。高良姜素增加了 T 细胞对 Hep3B/T 细胞共培养物中肿瘤细胞的杀伤作用。此外，高良姜素通过 PD-L1 抑制肿瘤细胞增殖、迁移和侵袭。体内实验表明，高良姜素抑制肿瘤生长。

结论

Galangin 通过 PD-L1 增强 T 细胞活性并抑制肿瘤细胞增殖、迁移和侵袭。目前的研究强调了高良姜素的抗肿瘤特性，为开发靶向 PD-L1 的肿瘤疗法提供了新的见解。