Licochalcone A inhibits proliferation and promotes apoptosis of colon cancer cell by targeting programmed cell death-ligand 1 via the NF-KB and Ras/Raf/MEK pathways
Licochalcone A inhibits proliferation and promotes apoptosis of colon cancer cell by targeting programmed cell death-ligand 1 via the NF-KB and Ras/Raf/MEK pathways
复制标题
甘草查尔酮 A 通过 NF-KB 和 Ras/Raf/MEK 通路靶向程序性细胞死亡配体 1，抑制结肠癌细胞增殖并促进其凋亡
DOI：
10.1016/j.jep.2021.113989
复制
发表时间：
2021-03-16
影响因子：
5.4
通讯作者：
Jin, Xuejun
中科院分区：
文献类型：
--
作者：
Liu, Xueshuang;Xing, Yue;Jin, Xuejun
民族药理意义：光叶甘草是一种传统药材，已有数千年的历史。临床应用广泛，已列入《中国药典》。甘草酮A是一种酚性查尔酮类化合物，是光果甘草特有的查尔酮类化合物，具有抗癌、抗炎、抗病毒、抗血管生成等多种药理活性。本研究目的：探讨甘草酮A的体内外抗肿瘤活性及其可能机制。材料与方法：采用分子对接、Western blotting、RT-PCR、流式细胞术、免疫荧光和免疫沉淀等方法研究甘草酮A体外抑制PD-L1表达的机制。采用T细胞与肿瘤细胞共培养模型检测细胞毒T淋巴细胞活性。采用集落形成、EDU标记和细胞凋亡实验检测细胞增殖和凋亡的变化。在体内，在HCT116细胞移植模型中评价了甘草酮A的抗肿瘤活性。结果：在本研究中，我们发现甘草酮A抑制程序性细胞死亡配体-1(PD-L1)的表达，而PD-L1在调节免疫反应中起关键作用。此外，甘草酮A还可抑制p65和RAS的表达。免疫沉淀实验表明，甘草酮A通过阻断p65和RAS之间的相互作用而抑制PD-L1的表达。在T细胞与肿瘤细胞共培养模型中，地塞米松A可增强细胞毒性T淋巴细胞的活性，恢复对肿瘤细胞的杀伤能力。此外，我们还发现，LICOCHALCONE A通过靶向PD-L1抑制细胞增殖，促进细胞凋亡。体内异种移植实验证实，甘草酮A具有抑制肿瘤移植瘤生长的作用。结论：总的来说，这些结果揭示了甘草酮A以前未知的性质，为该化合物的抗癌机制提供了新的见解。
Ethnopharmacological relevance: Glycyrrhiza glabra L., a traditional medicinal, has a history of thousands of years. It is widely used in clinic and has been listed in Chinese Pharmacopoeia. Licochalcone A is a phenolic chalcone compound and a characteristic chalcone of Glycyrrhiza glabra L. It has many pharmacological activities, such as anti-cancer, anti-inflammatory, anti-viral and anti-angiogenic activities.& nbsp; Aim of the study: In this study, we explored the anti-tumor activity and potential mechanism of licochalcone A in vitro and in vivo.& nbsp; Materials and methods: In vitro, the mechanism of licochalcone A at inhibiting PD-L1 expression was investigated by molecular docking, western blotting, RT-PCR, flow cytometry, immunofluorescence and immunoprecipitation assays. The co-culture model of T cells and tumor cells was used to detect the activity of cytotoxic T lymphocytes. Colony formation, EdU labelling and apoptosis assays were used to detect changes in cellular proliferation and apoptosis. In vivo, anti-tumor activity of licochalcone A was assessed in a xenograft model of HCT116 cells.& nbsp; Results: In the present study, we found that licochalcone A suppressed the expression of programmed cell death ligand-1 (PD-L1), which plays a key role in regulating the immune response. In addition, licochalcone A inhibited the expressions of p65 and Ras. Immunoprecipitation experiment showed that licochalcone A suppressed the expression of PD-L1 by blocking the interaction between p65 and Ras. In the co-culture model of T cells and tumor cells, licochalcone A pretreatment enhanced the activity of cytotoxic T lymphocytes and restored the ability to kill tumor cells. In addition, we showed that licochalcone A inhibited cell proliferation and promoted cell apoptosis by targeting PD-L1. In vivo xenograft assay confirmed that licochalcone A inhibited the growth of tumor xenografts.& nbsp; Conclusion: In general, these results reveal the previously unknown properties of licochalcone A and provide new insights into the anticancer mechanism of this compound.