吉非替尼对神经胶质瘤细胞移植瘤生长的影响和机制研究  

Effect of gefitinib on growth of glioma cell transplantation tumor and its mechanism

作　　者：崔乃浩 出良钊 Cui Naihao;Chu Liangzhao(Department of Neruosurgery,Affiliated Hospital of Guizhou Medical University,Guiyang 550001,Guizhou Province,China)

机构地区：[1]贵州医科大学附属医院神经外科,550001

出　　处：《中华老年心脑血管病杂志》2021年第8期867-871,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(81560409);贵州省科技计划项目(S120008)。

摘　　要：目的探究吉非替尼调控丝裂原激活的蛋白激酶(MEK)/细胞外调节蛋白激酶(ERK)通路对神经胶质瘤细胞移植瘤生长的影响及机制。方法通过皮下注射U87细胞的方法构建胶质瘤裸鼠模型,建模成功后将30只小鼠随机分为对照组、吉非替尼组和联合组(吉非替尼+MEK/ERK通路抑制剂PD98059),每组10只。建模28 d测量肿瘤体积和质量,通过检测Ki67、细胞周期蛋白D1(Cyclin D1)分析增殖水平,TUNEL染色检测凋亡。免疫组织化学染色检测CD34和血管内皮生长因子(VEGF)评估微血管密度和血管生成能力。并分析各组MEK和ERK mRNA和蛋白水平。结果吉非替尼组和联合组建模28 d肿瘤体积和质量明显低于对照组,且联合组建模28 d肿瘤体积和质量明显低于吉非替尼组(P<0.05)。吉非替尼组和联合组凋亡指数明显高于对照组[(18.54±2.75)%、(28.82±3.91)%vs(4.64±0.75)%,P<0.05],且联合组凋亡指数明显高于吉非替尼组(P<0.05)。吉非替尼组和联合组Cyclin D1、Ki67、微血管密度、VEGF表达明显低于对照组,且联合组Cyclin D1、Ki67、微血管密度、VEGF表达明显低于吉非替尼组(P<0.05)。吉非替尼组和联合组MEK、ERK mRNA和蛋白表达明显低于对照组,且联合组MEK、ERK mRNA和蛋白表达明显低于吉非替尼组(P<0.05)。结论吉非替尼可能通过MEK/ERK通路抑制胶质瘤细胞的增殖和血管生成,并诱导凋亡,从而起到抑制胶质瘤的作用。Objective To study the effect of gefitinib-regulated MEK/ERK signaling pathway on the growth of glioma cell transplantation tumor and its mechanism.Methods After the nude mouse model of glioma was established by subcutaneous injection with U87 cells, 30 mice were randomly divided into control group(n=10),gefitinib group(n=10) and gefitinib combined with MEK/ERK signaling pathway inhibitor PD98059 group(n=10).The tumor volume was measured and the tumor mass was assayed on day 28 after modeling.The proliferation of glioma cells was analyzed by detecting Ki67 and Cyclin D1.The apoptosis of glioma cells was tested with TUNEL staining.The CD34 and VEGF were detected with immunohistochemical staining for evaluating microvessel density and angiogenesis.The serum levels of MEK and ERK mRNA and protein in each group were analyzed.Results The tumor volume was significantly smaller and the tumor mass was significantly lighter in gefitinib group and gefitinib combined with MEK/ERK signaling pathway inhibitor PD98059 group than in control group, and in gefitinib combined with MEK/ERK signaling pathway inhibitor PD98059 group than in gefitinib group on day 28 after modeling.The apoptosis index of glioma cells was significantly higher in gefitinib group and gefitinib combined with MEK/ERK signaling pathway inhibitor PD98059 group than in control group(18.54%±2.75%,28.82%±3.91% vs 4.64%±0.75%,P<0.05),and in gefitinib combined with MEK/ERK signaling pathway inhibitor PD98059 group than in gefitinib group.The expression levels of Cyclin D1,Ki67,VEGF and microvessel density were significantly lower in gefitinib group and gefitinib combined with MEK/ERK signaling pathway inhibitor PD98059 group than in control group, and in gefitinib combined with MEK/ERK signaling pathway inhibitor PD98059 group than in gefitinib group(P<0.05).The expression levels of MEK and ERK mRNA and protein were significantly lower in gefitinib combined with MEK/ERK signaling pathway inhibitor PD98059 group than in gefitinib group(P<0.05).Conclusion Gefiti

关 键 词：神经胶质瘤 丝裂原激活蛋白激酶类 细胞增殖 血管内皮生长因子A 抗肿瘤药 

分 类 号：R739.41[医药卫生—肿瘤]