Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China.
Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China.
Phytomedicine. 2023 Jul 25;116:154877. doi: 10.1016/j.phymed.2023.154877. Epub 2023 May 20.
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.
To elucidate the anti-tumor mechanisms of galangin in vitro and in vivo.
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.
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.
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.
黄酮类化合物高良姜素（3,5,7-三羟基黄酮）来源于食用和药用草药益智的根。高良姜素具有许多生物活性，如抗炎、抗菌、抗病毒、抗肥胖和抗氧化作用。然而，高良姜素的抗肿瘤机制尚不清楚。
阐明高良姜素在体外和体内的抗肿瘤机制。
采用 MTT、western blot、免疫沉淀、RT-PCR 和免疫荧光检测评估高良姜素抑制 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、迁移和侵袭实验，以探讨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高良姜素的抗肿瘤作用。
高良姜素呈剂量依赖性抑制 PD-L1 表达，这在肿瘤进展中起主要作用。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 减少 PD-L1 表达。高良姜素增加了 Hep3B/T 细胞共培养物中 T 细胞对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。
高良姜素通过 PD-L1 增强 T 细胞活性并抑制肿瘤细胞增殖、迁移和侵袭。本研究强调了高良姜素的抗肿瘤特性，为开发针对 PD-L1 的肿瘤治疗药物提供了新的思路。
