川芎挥发油调控PI3K/Akt信号通路对胶质瘤细胞替莫唑胺耐药性的影响研究  

Impacts of Volatile Oil of Chuanxiong on Temozolomide Resistance in Glioma Cells by Regulating the PI3K/Akt Pathway

作　　者：路旭辉 周玲 郝玉梅 LU Xu-hui;ZHOU Ling;HAO Yu-mei(Department of Neurosurgery,Shijiazhuang Traditional Chinese Medicine Hospital,Shijiazhuang 050000,China;Department of Traditional Chinese Medicine,Hengshui People's Hospital,Hengshui 053200,China;Functional Department,Wukuang Hanxing Workers General Hospital,Handan 056005,China)

机构地区：[1]石家庄市中医院神经外科,石家庄050000 [2]衡水市人民医院中医科,衡水市053200 [3]五矿邯邢职工总医院衡水市功能科,邯郸056005

出　　处：《中国临床神经科学》2025年第1期10-18,共9页Chinese Journal of Clinical Neurosciences

基　　金：河北省2021年度中医药类科研计划课题(编号:2021194)。

摘　　要：目的分析川芎挥发油(CH)调控磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)信号通路对胶质瘤细胞替莫唑胺(TMZ)耐药性的影响.方法①构建U87 MG/TMZ耐药细胞株(U87 MG/TMZ细胞组),依据不同CH干预剂量分为:低剂量(L-CH)组(CH 20μmol·L^(-1))、中剂量(M-CH)组(CH 40μmol·L^(-1))、高剂量(H-CH)组(CH 80μmol·L^(-1))和IGF-1组(CH 80μmol·L^(-1)+IGF-1100 ng·mL^(-1)).观察各组细胞增殖、凋亡、迁移、侵袭情况以及细胞血管生成拟态情况,分析各组p-PI3K、caspase-3、p-mTOR、caspase-9、p-Akt蛋白表达水平.②构建脑胶质瘤模型,随机分为对照组(0.9%氯化钠溶液30 mg·kg^(-1),灌胃),TMZ组(TMZ 50 mg·kg^(-1),灌胃),CH组(CH 30 mg·kg^(-1),灌胃),TMZ+CH组(TMZ 50 mg·kg^(-1)+CH 30 mg·kg^(-1),灌胃).观察各组裸鼠肿瘤体积变化.结果与U87 MG/TMZ组比较,L-CH组、M-CH组、H-CH组细胞24、48、72 h增殖活力、克隆数、侵袭数、血管生成拟态数依次减少,细胞剩余划痕面积百分比、凋亡率依次增加(均P<0.05);与H-CH组比较,IGF-1组细胞24、48、72 h增殖活力、克隆数、侵袭数、血管生成拟态数增加,剩余划痕面积百分比、凋亡率减少(均P<0.05);与U87 MG/TMZ组比较,L-CH组、M-CH组、H-CH组p-PI3K、p-mTOR、p-Akt表达依次减少,caspase-3、caspase-9表达依次增加(均P<0.05);与H-CH组比较,IGF-1组p-PI3K、p-mTOR、p-Akt表达增加,caspase-3、caspase-9表达减少(均P<0.05);与对照组比较,TMZ组、CH组、TMZ+CH组肿瘤质量减少,TMZ+CH组肿瘤质量明显低于TMZ组和CH组(均P<0.05).结论CH可能抑制PI3K/Akt信号通路激活,进而减弱胶质瘤细胞TMZ耐药性.Aim To analyze the impacts of volatile oil of chuanxiong(CH)on temozolomide(TMZ)resistance in glioma cells by regulating the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)pathway.Methods TMZ resistant cell lines were constructed,and normally cultured.They were set as the U87 MG/TMZ group.U87 MG/TMZ cells treated with 20,40,and 80μmol·L^(-1)CH were set as the L-CH group,M-CH group,and H-CH group,respectively.U87 MG/TMZ cells treated with 80μmol·L^(-1)CH+100 ng·mL^(-1)IGF-1 were set as the IGF-1 group.The proliferation,apoptosis,migration,invasion,and vascular mimicry of cells in each group were observed,and the expression levels of p-PI3K,caspase-3,p-mTOR,caspase-9,and p-Akt proteins were analyzed.A glioma model was constructed and randomly separated into a blank group(30 mg·kg^(-1)saline gavage),a TMZ group(50 mg·kg^(-1)TMZ gavage),a CH group(30 mg·kg^(-1)CH gavage),and a TMZ+CH group(50 mg·kg^(-1)TMZ+30 mg·kg^(-1)CH gavage).The tumor volume changes of nude mice in each group were observed.Results Compared with the U87 MG/TMZ group,the proliferation activity,clone number,invasion number,and vascular mimicry number of cells in the L-CH group,M-CH group,and H-CH group at 24,48 and 72 hours decreased sequentially,while the percentage of remaining scratch area and apoptosis rate of cells increased sequentially(all P<0.05).Compared with the H-CH group,the proliferation activity,clone number,invasion number,and vascular mimicry number of cells in IGF-1 group at 24,48 and 72 hours increased sequentially,while the percentage of remaining scratch area and apoptosis rate of cells decreased sequentially(all P<0.05).Compared with the U87 MG/TMZ group,the expression of p-PI3K,p-mTOR,and p-Akt decreased sequentially in the L-CH group,M-CH group,and H-CH group,while the expression of caspase-3 and caspase-9 increased sequentially(all P<0.05).Compared with the H-CH group,the expression of p-PI3K,p-mTOR,and p-Akt increased in the IGF-1 group,while the expression of caspase-3 and caspase-9 decreased(all P<0.05

关 键 词：川芎挥发油 磷脂酰肌醇3激酶/蛋白激酶B信号通路 胶质瘤细胞 替莫唑胺 耐药性 

分 类 号：R730.264[医药卫生—肿瘤] Q189[医药卫生—临床医学]