蜂毒素通过下调F2RL1表达从而遏制胶质瘤细胞荷瘤小鼠肿瘤增殖的机制  

Melittin Inhibits Tumor Proliferation in Glioma-bearing Mice by Downregulating F2RL1 Expression

作　　者：王健伟 王俊[2] 刘昉[2] 戴珂 王超 WANG Jian-wei;WANG Jun;LIU Fang;DAI Ke;WANG Chao(College of Graduate,Zunyi Medical University,Zunyi,Guizhou,563000,China;Department of Neurosurgery,Guizhou Provincial People's Hospital,Guiyang,Guizhou,550000,China)

机构地区：[1]遵义医科大学研究生院,贵州遵义563000 [2]贵州省人民医院神经外科,贵州贵阳550000

出　　处：《现代生物医学进展》2023年第5期830-834,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81960454)。

摘　　要：目的:探讨蜂毒素通过下调F2RL1表达从而遏制胶质瘤细胞荷瘤小鼠肿瘤增殖的机制。方法:40只雄性NOD/SCID小鼠(5周龄,15-18 g)购自北京维塔河实验动物技术公司。实验前,让小鼠适应环境一周。NOD/SCID小鼠在右侧海马体中注射了2×10^(5)U87-MG细胞建立异种移植模型。当肿瘤体积增长到100 mm^(3)时,将小鼠随机分为模型组(空腹注射生理盐水)和蜂毒素组(腹腔注射5 mg/kg蜂毒素),每组20只小鼠。在第5天(注射的第5天)、第10天、第15天每次处死5只小鼠,通过实时PCR分析小鼠肿瘤组织中F2RL1、Bcl-2、Bax和Capase-3的mRNA表达。使用卡尺测量荷瘤小鼠肿瘤体积,使用电子天平对肿瘤组织进行称重测量。通过蛋白印迹分析肿瘤组织中p-PI3K、p-AKT和p-mTOR的蛋白表达。通过TUNEL染色检测人脑肿瘤中凋亡细胞的百分比。结果:蜂毒素组F2RL1 mRNA表达较模型组降低(P<0.05),蜂毒素抑制F2RL1 mRNA表达。第5 d、10 d和15 d测得肿瘤体积发现蜂毒素肿瘤体积较模型组减小(P<0.05)。第5 d、10 d和15 d测得肿瘤体积发现蜂毒素肿瘤重量较模型组减轻(P<0.05)。蜂毒素组p-PI3K、p-AKT和p-mTOR的蛋白表达较模型组降低(P<0.05)。蜂毒素组Bax和Capase-3的mRNA表达较模型组降低(P<0.05),蜂毒素组Bcl-2 mRNA表达较模型组升高(P<0.05)。蜂毒素组TUNEL阳性细胞的百分比较较模型组升高(P<0.05)。结论:蜂毒素通过下调肿瘤小鼠体内F2RL1表达抑制PI3K/AKT信号通路激活,促进了体内肿瘤细胞凋亡,从而有效抑制经胶质瘤细胞的生长、增殖。Objective:To investigate the mechanism of melttin inhibiting tumor proliferation in glioma cell tumor-bearing mice by down-regulating the expression of F2RL1.Methods:Forty male NOD/SCID mice(5 weeks old,15-18 g)were purchased from Beijing Weitahe Laboratory Animal Technology Company.Mice were acclimated to the environment for a week before the experiment.NOD/SCID mice were injected with 2×10^(5) U87-MG cells in the right hippocampus to establish a xenograft model.When the tumor volume increased to 100 mm,the mice were randomly divided into model group(injected with normal saline on an empty stomach)and melittin group(injected with 5 mg/kg melitin intraperitoneally),20 mice in each group.Five mice were sacrificed each time on day 5(day 5 of injection),day 10,and day 15.The mRNA expression of F2RL1,Bcl-2,Bax and Capase-3 in mouse tumor tissues was analyzed by real-time PCR.The tumor volume of the tumor-bearing mice was measured using calipers,and the tumor tissue was weighed using an electronic balance.The protein expression of p-PI3K,p-AKT and p-mTOR in tumor tissues was analyzed by Western blotting.The percentage of apoptotic cells in human brain tumors was detected by TUNEL staining.Results:The expression of F2RL1 mRNA in the melttin group was lower than that in the model group(P<0.05),and melittin inhibited the expression of F2RL1 mRNA.The tumor volume measured on the 5th,10th and 15th days showed that the melittin tumor volume was reduced compared with the model group(P<0.05).The tumor volume was measured on the 5th,10th and 15th days,and the melittin tumor weight was reduced compared with the model group(P<0.05).The protein expressions of p-PI3K,p-AKT and p-mTOR in the melittin group were lower than those in the model group(P<0.05).The mRNA expressions of Bax and Capase-3 in the melittin group were lower than those in the model group(P<0.05),and the mRNA expression of Bcl-2 in the melitin group was higher than that in the model group(P<0.05).The percentage of TUNEL positive cells in the melitin group was hig

关 键 词：蜂毒素 F2RL1 胶质瘤细胞 荷瘤小鼠 细胞凋亡 

分 类 号：R-33[医药卫生] R730.264