青藤碱基于CASC11/AKT3轴对脑胶质瘤原位荷瘤裸鼠肿瘤生长及血管生成的抑制作用  

Inhibition effect of Sinomenine based on CASC11/AKT3 axis on tumor growth and angiogenesis for in situ tumor-bearing nude mice with brain glioma

作　　者：祁大勇 刘军 赵志煌[3] 李刚[3] 韩永刚 QI Da-yong;LIU Jun;ZHAO Zhi-huang;LI Gang;HAN Yong-gang(Department of Neurosurgery,Tangshan Workers′Hospital,Tangshan 063000,Hebei,China;Department of Neurosurgery,Handan First Hospital,Handan 056000,Hebei,China;Department of Neurosurgery,Cangzhou Central Hospital,Cangzhou 061000,Hebei,China)

机构地区：[1]河北省唐山市工人医院神经外科,河北省唐山市063000 [2]河北省邯郸市第一医院神经外科,河北省邯郸市056000 [3]河北省沧州市中心医院神经外科,河北省沧州市061000

出　　处：《广西医学》2022年第12期1373-1377,共5页Guangxi Medical Journal

基　　金：河北省医学科学研究课题计划(20200312)。

摘　　要：目的观察青藤碱对脑胶质瘤原位荷瘤裸鼠肿瘤生长及组织血管生成的抑制作用,并基于癌易感候选基因11(CASC11)/丝氨酸/苏氨酸激酶3(AKT3)探讨相关机制。方法取对数生长期U87-MG细胞,将CASC11过表达质粒CASC11 mimics转染至U87-MG细胞,48 h后用于后续实验。取45只BALB/c裸鼠,随机抽取10只设为空白组;其余25只裸鼠给予U87-MG细胞悬液建立脑胶质瘤原位荷瘤模型,将成功建模的20只裸鼠随机分为脑胶质瘤组、青藤碱组,各10只;剩余的10只裸鼠注射转染48 h后的U87-MG细胞悬液,设为mimics联合青藤碱组。建模完成后7 d,给予青藤碱组、mimics联合青藤碱组裸鼠腹腔注射青藤碱(20 mg/kg),其余组腹腔注射等体量生理盐水。干预14 d后,测定抑瘤率与脾脏指数,检测肿瘤组织的微血管密度和AKT3蛋白的表达量。结果mimics联合青藤碱组、青藤碱组的抑瘤率分别为(30.29±4.46)%、(52.10±6.87)%,前者较后者降低(P<0.05)。与空白组相比,脑胶质瘤组的脾脏指数降低(P<0.05);与脑胶质瘤组比较,青藤碱组的脾脏指数升高,血管密度、AKT3蛋白的表达量均降低(均P<0.05);与青藤碱组比较,mimics联合青藤碱组的脾脏指数降低,血管密度、AKT3蛋白的表达量均升高(均P<0.05)。结论青藤碱可提升脑胶质瘤原位荷瘤裸鼠的免疫功能,抑制肿瘤血管生成和肿瘤生长,其可能通过抑制CASC11表达进而下调AKT3蛋白表达来发挥作用。Objective To observe the inhibition effects of Sinomenine on tumor growth and tissue angiogenesis for in situ tumor-bearing nude mice with brain glioma,and to explore related mechanisms based on cancer susceptibility candidate 11(CASC11)/Serine/threonine kinase 3(AKT3).Methods U87-MG cells in logarithmic phase were obtained.The CASC11-overexpressied plasmid CASC11 mimics was transfected into U87-MG cells and was used for follow-up experiments after 48 hours.A total of 45 BALB/c nude mice were obtained,and 10 of them were randomly selected as the blank group,whereas the remaining 25 nude mice were given U87-MG cell suspension to establish brain glioma in situ tumor-bearing model.Twenty nude mice,which were successfully modeled,were randomly assigned to the brain glioma group or Sinomenine group,with 10 mice in each group.The remaining 10 nude mice receiving injection of U87-MG cell suspension after 48 hours of transinfection,were set as the mimics combined with Sinomenine group.Seven days after modeling completion,nude mice in the Sinomenine and mimics combined with Sinomenine groups were given intraperitoneal injection of Sinomenine(20 mg/kg),whereas the remaining groups were given intraperitoneal injection of equivalent volume of normal saline.After 14 days of intervention,the rate of tumor inhibition and spleen index were measured,microvessel density and AKT3 protein expression were detected in tumor tissues.Results The rates of tumor inhibition in the mimics combined with Sinomenine and Sinomenine groups were(30.29±4.46)%,and(52.10±6.87)%,respectively,and the former was lower than the latter(P<0.05).Compared with the blank group,the spleen index in the brain glioma group was decreased(P<0.05).In the comparison of the brain glioma group,the Sinomenine group exhibited elevated index of spleen,whereas declines of microvessel density and AKT3 protein expression(all P<0.05).The mimics combined with Sinomenine group interpreted decline of spleen index,while elevated microvessel density and AKT3 protein expression

关 键 词：脑胶质瘤 青藤碱 血管生成 肿瘤生长 免疫功能 癌易感候选基因11 丝氨酸/苏氨酸蛋白激酶3 原位荷瘤裸鼠模型 

分 类 号：R739.41[医药卫生—肿瘤]