瑞芬太尼调节AKT/GSK-3β/Snail信号通路对肺癌细胞增殖、凋亡和上皮间质转化的影响  

Impacts of remifentanil on the proliferation, apoptosis, and epithelial-mesenchymal transformation of lung cancer cells by regulating AKT/GSK-3β/Snail signaling pathway

作　　者：王豆豆[1] 张明明[1] 周彬 WANG Doudou;ZHANG Mingming;ZHOU Bin(Qingdao Eighth People s Hospital,Qingdao,Shandong 266100,China)

机构地区：[1]青岛市第八人民医院,山东青岛266100

出　　处：《临床肺科杂志》2025年第1期98-103,共6页Journal of Clinical Pulmonary Medicine

基　　金：青岛市科技成果项目(青科评备字第2021050314号)。

摘　　要：目的 探究瑞芬太尼(RF)调节蛋白激酶B(AKT)/糖原合成酶激酶3β(GSK-3β)/Snail信号通路对肺癌细胞增殖、凋亡和上皮间质转化(EMT)的影响。方法 将非小细胞肺癌细胞A549分为低(RF-L)、中(RF-M)、高浓度RF(RF-H)组(10、20、40 nmol/L RF)、高浓度RF+AKT激活剂SC79(RF-H+SC79)组(40 nmol/L RF+4μg/mL SC79)和对照组(Control组)。CCK-8法检测细胞增殖能力。划痕实验检测细胞迁移能力。Transwell实验检测细胞侵袭能力。流式细胞术测量细胞凋亡。实时荧光定量PCR测定AKT、GSK-3β、Snail mRNA水平。Western Blot测定蛋白表达。结果 相较于Control组,RF-M、RF-H组48和72 h的OD450、细胞侵袭数目、划痕愈合率、AKT、GSK-3β、Snail mRNA和蛋白表达、Bcl-2蛋白、EMT相关蛋白N-cadherin、Vimentin表达显著降低(P<0.05),细胞凋亡率、Bax蛋白、E-cadherin蛋白表达显著升高(P<0.05)。SC79减弱了RF对肺癌细胞增殖和EMT进程的抑制作用,减弱细胞凋亡。结论 RF可阻碍肺癌细胞EMT和增殖,诱导凋亡,这可能与AKT/GSK-3β/Snail信号通路的抑制相关。Objective To investigate the impacts of remifentanil(RF)on the proliferation,apoptosis,and epithelial-mesenchymal transformation(EMT)of lung cancer cells by regulating protein kinase B(AKT)/glycogen synthase kinase-3β(GSK-3β)/Snail signal pathway.Methods Non-small cell lung cancer A549 cells were grouped into low(RF-L),medium(RF-M),high RF(RF-H)groups(10,20,40 nmol/L RF),high RF+AKT activator SC79(RF-H+SC79)group(40 nmol/L RF+4μg/mL SC79),and control group.CCK-8 method was applied to detect cell proliferation.The cell migration ability was detected by scratch test.A transwell test was applied to detect the invasion ability of cells.The apoptosis was detected by flow cytometry.The expression levels of AKT,GSK-3β,and Snail mRNA were measured by real-time fluorescence quantitative PCR.Western blot was used to detect the expression of the protein.Results Compared with the control group,the OD 450 at 48 and 72 h,cell invasion numbers,wound healing rate,AKT,GSK-3β,Snail mRNA and protein expression,Bcl-2 protein,EMT-related protein N-cadherin,and Vimentin expression were significantly lower in the RF-M and RF-H groups(P<0.05),while the cell apoptosis rate and Bax protein,E-cadherin protein expression were significantly higher(P<0.05).SC79 attenuated the inhibitory effect of RF on the proliferation and EMT process of lung cancer cells,and attenuated cell apoptosis.Conclusion RF can inhibit EMT and proliferation of lung cancer cells and induce apoptosis,which may be related to the inhibition of the AKT/GSK-3β/Snail signaling pathway.

关 键 词：瑞芬太尼 蛋白激酶B/糖原合成酶激酶3β/Snail信号通路 肺癌 上皮间质转化 

分 类 号：R734.2[医药卫生—肿瘤]