中国临床药理学杂志2024，Vol.40Issue(8)：1150-1154,5.DOI:10.13699/j.cnki.1001-6821.2024.08.013
替莫唑胺联合EZH2抑制药GSK343对垂体瘤GH3细胞体外侵袭性的影响
Effect of temozolomide combined with EZH2 inhibitor GSK343 on the invasivity of GH3 cells in pituitary tumor in vitro
摘要
Abstract
Objective To investigate the effect of temozolomide(TMZ)combined with histone methyltransferase enhancer of Zeke 2(EZH2)inhibitor GSK343 on apoptosis and invasion of GH3 cells and its mechanism.Methods Different concentrations of TMZ treated cells were used to screen TMZ treated dose.GH3 cells were randomly divided into blank group,TMZ-L group(200 μmol·L-1 TMZ),TMZ-H group(400 μmol·L-1 TMZ),GSK343 group(20 μmol·L-1 GSK343)and TMZ+GSK343 group(400 μmol·L-1+20 μmol·L-1 GSK343).After 48 h of drug treatment,cell counting kit-8(CCK-8)assay was used to detect cell survival rate;terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL)and flow cytometry were used to detect cell apoptosis;Transwell assay was used to detect cell invasion ability;Western blot assay was used to detect cell-related protein expression.Results TUNEL positive cell rates in blank group,TMZ-L group,TMZ-H group,GSK343 group and TMZ+GSK343 group were(4.31±0.71)％,(15.36±0.91)％,(22.26±2.13)％,(13.05±0.71)％and(34.55±3.75)％;cell invasion numbers were(247.67±27.23),(183.00±20.66),(152.11±8.82),(182.89±18.24)and(116.11±12.73)cells;the expression levels of Bax protein were 0.44±0.05,0.58±0.06,0.81±0.07,0.66±0.06 and 1.03±0.06;the expression of E-cadherin protein were 0.33±0.05,0.57±0.05,0.84±0.12,0.59±0.07 and 1.00±0.12;Vimentin protein expression levels were 0.91±0.14,0.72±0.09,0.62±0.07,0.77±0.08 and 0.47±0.04;phosphorylated phosphatidyl alcohol 3-kinase(p-PI3K)protein expression levels were 0.99±0.11,0.86±0.06,0.68±0.07,0.72±0.08 and 0.52±0.08;phosphorylated protein kinase B(p-AKT)protein expression levels were 1.01±0.06,0.71±0.07,0.57±0.05,0.80±0.07 and 0.43±0.04.TMZ-L group,TMZ-H group,GSK343 group and TMZ+GSK343 group had significant differences in the above indexes compared with blank group(all P＜0.05);TMZ+GSK343 group was compared with TMZ-L group TM2-H group or GSK343 group,and the above indexes were significantly difference(all P＜0.05).Conclusion TMZ combined with EZH2 inhibitor GSK343 can significantly inhibit GH3 cell invasion and induce apoptosis,which may be related to the regulation of PI3 K/AKT pathway.关键词
替莫唑胺/zeste基因增强子类同源物2/垂体瘤/细胞侵袭/细胞凋亡/上皮间质转化Key words
temozolomide/histone methyltransferase enhancer of Zeke 2/pituitary tumor/cell invasion/cell apoptosis/epithelial mesenchymal transformation分类
医药卫生引用本文复制引用
张俊,路长宇,付佳,王静,王斌,梁剑峰..替莫唑胺联合EZH2抑制药GSK343对垂体瘤GH3细胞体外侵袭性的影响[J].中国临床药理学杂志,2024,40(8):1150-1154,5.基金项目
吴阶平医学基金会临床科研专项基金资助项目(320.6750.2023-11-7) （320.6750.2023-11-7）
