地昔帕明调控低氧诱导因子1α信号通路对人脑胶质瘤增殖凋亡的影响  

Mechanism of desipramine on proliferation and apoptosis of human glioma by regulating HIF-1αsignaling pathway

作　　者：陈佩雷 郑建晓 周子晔[3] 胡梦雪 

机构地区：[1]温州医科大学附属乐清人民医院西药房,浙江温州325600 [2]温州医科大学附属乐清人民医院肿瘤内科,浙江温州325600 [3]温州医科大学附属第一医院药物临床试验中心,浙江温州325600

出　　处：《中国药物与临床》2025年第7期429-433,I0002,共6页Chinese Remedies & Clinics

基　　金：浙江省温州市基础性科研项目(Y20240381)。

摘　　要：目的探究不同浓度地昔帕明调控低氧诱导因子1α(HIF-1α)信号通路对人脑胶质瘤增殖、凋亡的影响。方法正常培养胶质瘤U87细胞,采用随机数字表法随机分为对照组、地昔帕明干预组(低、中、高剂量),其中对照组加入不含地昔帕明的培养基,干预组分别加入含20、30、40μmol/L地昔帕明的培养基。采用细胞计数试剂盒-8(CCK-8)法检测细胞活性,细胞克隆实验检测细胞增殖能力,流式细胞术检测细胞凋亡,三维培养技术观察细胞血管生成拟态状态,蛋白免疫印迹法检测HIF-1α、表皮生长因子受体(EGFR)和血管内皮生长因子A(VEGFA)蛋白表达。结果各组细胞存活率、克隆形成数、细胞凋亡率的比较,差异有统计学意义(F=106.253、12.881、180.742,P<0.05)。30、40μmol/L地昔帕明干预组细胞存活率、克隆形成数低于对照组,细胞凋亡率高于对照组(P<0.05)。各组血管生成拟态计数的比较,差异有统计学意义(F=32.063,P<0.05)。30、40μmol/L地昔帕明干预组血管生成拟态计数低于对照组(P<0.05)。各组U87细胞HIF-1α信号通路(HIF-1α、EGFR和VEGFA)蛋白表达的比较,差异有统计学意义(P<0.05);其中30、40μmol/L地昔帕明干预组低于对照组(P<0.05)。结论地昔帕明可抑制人脑胶质瘤细胞U87的增殖和血管生成拟态形成,诱导细胞凋亡,其机制可能与抑制HIF-1α、EGFR和VEGFA表达有关。Objective To explore the effects of different concentrations of desipramine on proliferationand apoptosis of human glioma by regulating hypoxia-inducible factor 1α(HIF-1α)signaling pathway.MethodsGlioma U87 cells were cultured normally and randomly divided into a control group and desipramine interventiongroups(low,medium and high doses).The control group received culture medium without desipramine,while theintervention groups were treated with 20,30,and 40μmol/L desipramine,respectively.The cells activity was de-tected by Cell Counting Kit-8(CCK-8),cell proliferation ability was detected by cell clone assay,cell apoptosiswas detected by flow cytometry,cells vasculogenic mimicry was observed by three-dimensional culture technique,and expressions of HIF-1α,epidermal growth factor receptor(EGFR)and vascular endothelial growth factor A(VEGFA)were detected by Western blot.Results There were significant differences in cells survival rate,num-ber of clone formation and apoptosis rate among all groups(F=106.253,12.881,180.742,all P<0.05).The cellssurvival rate and number of clone formation in 30 and 40μmol/L desipramine intervention groups were signifi-cantly lower than those in control group,and apoptosis rate was significantly higher than that in control group(P<0.05).There were significant differences in the count of vasculogenic mimicry among all groups(F=32.063,P<0.05).The count of vasculogenic mimicry in 30 and 40μmol/L desipramine intervention groups was significantlylower than that in control group(P<0.05).There were significant differences in expressions of HIF-1αsignalingpathway related proteins(HIF-1α,EGFR and VEGFA)in U87 cells among all groups(P<0.05),and which in 30and 40μmol/L desipramine intervention groups were lower than those in control group(P<0.05).ConclusionDesipramine can inhibit proliferation of human glioma cells U87 and formation of vasculogenic mimicry,induceapoptosis,and the mechanism may be related to inhibiting expressions of HIF-1α,EGFR and VEGFA.

关 键 词：地昔帕明 神经胶质瘤 增殖 凋亡 血管生成拟态 低氧诱导因子1α信号通路 

分 类 号：R739.4[医药卫生—肿瘤] R739.41[医药卫生—临床医学]