吴茱萸碱对宫颈癌小鼠移植瘤的抑制机制  

The inhibitory mechanism of evodialine in mice with cervical cancer transplantation

作　　者：蔡月红 麦燕 钱沁佳 CAI Yuehong;MAI Yan;QIAN Qinjia(Department of Obstetrics and Gynecology,Sanya Central Hospital,Sanya 572000,China)

机构地区：[1]三亚中心医院妇产科,三亚572000

出　　处：《西北药学杂志》2024年第5期77-82,共6页Northwest Pharmaceutical Journal

基　　金：海南省卫生计生行业科研项目(编号:18A200164)。

摘　　要：目的 探究吴茱萸碱(evodiamine,Evo)对宫颈癌小鼠移植瘤的抑制作用及对哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)/p70核糖体蛋白S6激酶(p70 ribosomal protein S6 kinase, p70S6K)通路的影响。方法 取40只BALB/c裸鼠,随机选取10只设为健康组,剩余30只裸鼠成功建立宫颈癌移植瘤模型,随机分为荷瘤组、Evo组和Evo联合溶血磷脂酸(lysophosphatidic acid,LPA)组,各10只。Evo联合LPA组裸鼠灌胃Evo(18 mg·kg^(-1)),尾静脉注射LPA(0.8μmol·kg^(-1));Evo组裸鼠灌胃Evo(18 mg·kg^(-1)),尾静脉注射等体积生理盐水;健康组、荷瘤组裸鼠灌胃等体积二甲基亚砜(dimethyl sulfoxide,DMSO),尾静脉注射等体积生理盐水。每日1次,连续30 d。测定肿瘤体积;流式细胞仪检测外周血CD4^(+)、CD8^(+)T淋巴细胞占比;Tunel染色检测移植瘤细胞凋亡率;免疫印记法(Western blotting)检测移植瘤组织mTOR、p-mTOR、p70S6K、p-p70S6K蛋白的表达水平。结果 与荷瘤组比较,Evo组干预后第10、20、30天肿瘤体积均减小,CD4^(+)T淋巴细胞占比、CD4^(+)/CD8^(+)值升高,CD8^(+)T淋巴细胞占比、p-mTOR/mTOR值和p-p70S6K/p70S6K值降低(P<0.05);与Evo组比较,Evo联合LPA组干预后第10、20、30天肿瘤体积均增大,CD4^(+)T淋巴细胞占比、CD4^(+)/CD8^(+)值降低,CD8^(+)T淋巴细胞占比、p-mTOR/mTOR值和p-p70S6K/p70S6K值升高(P<0.05)。结论 Evo可抑制宫颈癌移植瘤生长、促进宫颈癌细胞凋亡、增强机体免疫功能,其作用机制可能与抑制mTOR/p70S6K信号通路有关。Objective To investigate the inhibitory effect of evodiamine(Evo)on transplanted tumor in mice with cervical cancer and its effects on mammalian target of rapamycin(mTOR)/p70 ribosomal protein S6 kinase(p70S6K)pathway.Methods Among 40 BALB/c nude mice,10 were randomly used as healthy group,and the rest were used to establish cervical cancer xenograft model.Thirty mice were successfully modeled and randomly divided into tumor-bearing group,Evo group,and Evo combined with lysophosphatidic acid(LPA)group,each with 10 rats.The mice in the Evo combined LPA group were given Evo(18 mg·kg^(−1))intragastrically and LPA(0.8μmol·kg−1)was injected into the tail vein.The mice in the Evo group were administered with Evo(18 mg·kg−1)intragastrically,and an equal volume of normal saline was injected into the tail vein.The mice in healthy group and tumor-bearing group were given an equal volume of dimethyl sulfoxide(DMSO)by intragastric administration,and an equal volume of normal saline was injected into the tail vein.Once a day,the intervention lasted for 30 days.The tumor volume was measured.Flow cytometry was used to detect the proportion of CD4^(+)and CD8^(+)T lymphocytes in peripheral blood.Tunel staining was used to detect the apoptosis rate of transplanted tumor cells.Western blot method was used to detect the protein expression of mTOR,pmTOR,p70S6K,and p-p70S6K in transplanted tumor tissues.Results Compared with the tumor-bearing group,the tumor volumes were decreased on the 10th,20th,and 30th day after intervention,the proportions of CD4^(+)T lymphocytes,CD4^(+)/CD8^(+)ratio were increased,and the proportions of CD8^(+)T lymphocytes,p-mTOR/mTOR,p-p70S6K/p70S6K were decreased in the Evo group(P<0.05).Compared with the Evo group,the tumor volumes were increased on the 10th,20th,and 30th day after intervention,the proportions of CD4^(+)T lymphocytes,CD4^(+)/CD8^(+)ratio were decreased,and the proportions of CD8^(+)T lymphocytes,p-mTOR/mTOR,p-p70S6K/p70S6K were increased in the Evo combined with LPA group(P<0.05).C

关 键 词：吴茱萸碱 宫颈癌 哺乳动物雷帕霉素靶蛋白 核糖体40S小亚基S6K蛋白激酶 信号通路 

分 类 号：R966[医药卫生—药理学]