Abstract：Objective: To investigate the influences of GSK343 on the enhancer of Zeste homolog 2 (EZH2)/signal transducer and activator of transcription 4 (STAT4)/interferon-γ (IFN-γ) pathway and the killing effect of γδT cells. Methods: Human glioma cell line U373 was cultured in vitro, and the control group (normal cell cultured, no drug treatment) and GSK343 group (GSK343 treatment) were set up. The proliferation of U373 cells and the killing effect of γδT cells on U373 cells were detected by CCK-8 method; the apoptosis of U373 cells was detected by flow cytometry; the cell morphology was observed by microscopy; and the expressions of EZH2, p-STAT4 and IFN-γ proteins in U373 cells were detected by Western blot. Results: With the increase of GSK343 concentration, the inhibition rate of U373 cell proliferation increased gradually, and the GSK343 half inhibition concentration (IC50) of U373 cells was in the range of 20-50 μmol/L. Therefore, 50μmol/L were selected as the best treatment concentration in the GSK343 group for subsequent experiments. Compared with the control group, the expression levels of EZH2 protein in GSK343 group decreased significantly (P<0.05), and the apoptosis rate, p-STAT4, IFN-γ protein expression level and the killing activity of γδT cells to U373 cells in each group were significantly increased (P<0.05), irregular morphology and cytoplasmic swelling U373 cells killing of γδT cells increased. Conclusion: GSK343 can inhibit the expressions of EZH2 proteins, promote the expression of STAT4 phosphorylation and IFN-γ protein, thus enhancing the killing effect of γδT cells on U373 cells, inhibit the proliferation and induce apoptosis of U373 cells.
夏丽琼, 杨明华, 谢燕. EZH2抑制剂GSK343对脑胶质瘤细胞EZH2/STAT4/IFN-γ通路及γδT细胞杀伤作用的影响[J]. 河北医学, 2022, 28(6): 904-908.
XIA Liqiong, YANG Minghua, XIE Yan. Influences of GSK343 on EZH2/STAT4/IFN-γ Pathway and the Killing Effect of γδT Cells in Glioma Cells. HeBei Med, 2022, 28(6): 904-908.
[1] Champeaux C,Houston D,Dunn L.Atypical meningioma.A study on recurrence and disease-specific survival[J].Neurochirurgie,2017,63(4):273-281. [2] Hwang KL,Hwang WL,Bussiere MR,et al.The role of radiotherapy in the management of high-grade meningiomas[J].Chin Clin Oncol,2017,6(Suppl 1):1-11. [3] 张光辉,邵小燕,严小敏,等.γδT细胞的体外扩增及对不同肿瘤细胞的杀伤性研究[J].国际肿瘤学杂志,2018,45(8):449-452. [4] 张娟,冯燕,和水祥.MicroRNA-98通过下调EZH2表达抑制结直肠癌细胞的活力与侵袭能力[J].中国病理生理杂志,2019,35(1):68-74. [5] Xue YL,Zhang SX,Zheng CF,et al.Silencing of STAT4 protects against autoimmune myocarditis by regulating Th1/Th2 immune response via inactivation of the NF-κB pathway in rats[J].Inflammation,2019,42(4):1179-1189. [6] Xu H,Zhang L,Qian X,et al.GSK343 induces autophagy and downregulates the AKT/mTOR signaling pathway in pancreatic cancer cells[J].Exp Ther Med,2019,18(4):2608-2616. [7] 许有忠,田作春,李才.MicroRNA-204在非小细胞肺癌患者组织中的表达及对癌细胞增殖和凋亡的影响[J].中国现代医学杂志,2018,28(4):57-61. [8] 王佳林,云升,邱英.γδT细胞的抗肿瘤免疫治疗研究进展[J].内蒙古医学杂志,2020,52(8):916-919. [9] Ma J,Zhang J,Weng YC,et al.EZH2-mediated microR NA-139-5p regulates epithelial-mesenchymal transition and lymph node metastasis of pancreatic cancer[J].Mol Cells,2018,41(9):868-880 [10] Yi X,Guo J,Guo J,et al.EZH2-mediated epigenetic silencing of TIMP2 promotes ovarian cancer migration and invasion[J].Sci Rep,2017,7(1):3568-3583. [11] 丁沐阳,蒋文军,张力,等.EZH2抑制剂对宫颈癌HeLa细胞的抑制作用[J].西安交通大学学报:医学版,2015,36(5):633-681. [12] 宋振宇,刘献志,刘增进,等.包含溴结构域的蛋白9调控神经胶质瘤增殖和迁移及细胞因子信号转导抑制因子3/信号转导与转录激活因子3信号转导[J].中华实验外科杂志,2021,38(5):847-850.. [13] 沈娟,吴琼丽,杨滨燕,等.IL-12逆转顺铂对人NK细胞免疫功能的抑制及其机制[J].中国肿瘤生物治疗杂志,2018,25(9):872-877. [14] Liu TP,Hong YH,Tung KY,et al.In silico and experimental analyses predict the therapeutic value of an EZH2 inhibitor GSK343 against hepatocellular carcinoma through the induction of metallothionein genes[J].Oncoscience,2016,3(1):9-20. [15] 赵珺,吴昆仑,吴琼丽,等.托法替尼对HMBPP特异性γδT细胞功能影响的研究[J].国际免疫学杂志,2018,41(6):591-598.
2022, Vol. 28 
冀公网安备13080202000677号