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miR-21通过下调PTEN增强人脑胶质瘤细胞对卡莫司汀耐药
  • ISSN号:1000-4718
  • 期刊名称:中国病理生理杂志
  • 时间:2012
  • 页码:1345-1351
  • 分类:R739.4[医药卫生—肿瘤;医药卫生—临床医学]
  • 作者机构:[1]暨南大学医学院病理学系,广东广州510632
  • 相关基金:国家自然科学基金资助项目(No.81072059;No.81101652);广东省高等学校科技创新重点项目(No.CXZDlll0)
  • 相关项目:IL-6/CD130对脑胶质瘤获得性耐药的调控机制
中文摘要:

探讨微小RNA-21(miR-21)在增强人脑胶质瘤细胞对卡莫司汀(BCNU)耐药中的作用及其可能的作用机制。方法:用jetPRIME将miR-21mimics及阴性对照序列转入人脑胶质瘤细胞SWOZ2,用实时荧光定量PCR法检测BCNU敏感株SWOZ2与BCNU耐药株SWOZ2-BCNU、SWOZ2-miR-21mimics细胞与对照组细胞中miR-21表达差异,用CCK-8检测这两对细胞对BCNU敏感度的差异,用Westernblotting检测这两对细胞中第10号染色体同源缺失性磷酸酶及张力蛋白(PTEN)、磷酸化蛋白激酶B(P—Akt)和P-糖蛋白(P—gP)表达的差异。结果:SWOZ2-BCNU细胞miR-21的表达水平明显高于SWOZ2细胞,转染组SWOZ2-miR-21mim—ics细胞中miR-21的表达量明显高于对照组;SWOZ2-BCNU细胞BCNU的半数抑制浓度(Ic50)明显高于SWOZ2细胞,转染组细胞BCNU的Ic。明显高于对照组;与SWOZ2细胞相比,SWOZ2-BCNU细胞中PTEN蛋白的表达明显降低,P—Akt和P—gp蛋白的表达都明显升高;转染后,与对照组相比,转染组细胞中PTEN蛋白的表达明显降低,而P—Akt和P—gP蛋白的表达皆明显升高。结论:miR-21可能通过下调PTEN蛋白表达,增强人脑胶质瘤细胞对BCNU耐药。

英文摘要:

AIM: To explore the function of miR - 21 in human glioma cells resistant to carmustine[ 1,3 - bis (2 -chloroethyl) -1 -nitrosourea, BCNU ] and to elucidate its related mechanism. METHODS: SWOZ2 cells were transfected with miR -21 mimics (SWOZ2 -miR -21 mimics) or miRNA mimics negative control (control group) by the method of jetPRIME. The real - time fluorescence quantitative PCR was used to detect and compare the levels of miR - 21 expression between BCNU - resistant cell line SWOZ2 - BCNU and BCNU - sensitive cell line SWOZ2, or between SWOZ2 - miR - 21 mimic group and control group. The drug sensitivity of these cells to BCNU was determined by CCK - 8 assay. The protein expression of phosphatase and tensin homology deleted on chromosome 10 (PTEN), phosphorylated protein ki- nase B (p- Akt) and P- glycoprotein (P- gp) in these cells were also detected by Western blotting. RESULTS: The expression level of miR - 21 was remarkably higher in SWOZ2 - BCNU cells than that in SWOZ2 cells. The expression lev- el of miR-21 was significantly higher in SWOZ2 -miR-21 mimics group than that in control group. The half- maximal inhibitory concentration (ICw ) of BCNU was obviously higher for SWOZ2 - BCNU cells than that for SWOZ2 ceils. The ICso of BCNU was markedly higher in SWOZ2 - miR - 21 mimics group than that in control group. PTEN protein expression was remarkably lower, but p - Akt and P - gp protein expression levels were markedly higher in SWOZ2 - BCNU cells than those in SWOZ2 cells. The protein level of PTEN was significantly lower, but the protein levels of p - Akt or P - gp were distinctly higher in SWOZ2 -miR -21 mimics group than those in control group. CONCLUSION: miR -21 enhances the resistance of human glioma cells to BCNU by down - regulating the expression of PTEN protein.

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期刊信息
  • 《中国病理生理杂志》
  • 中国科技核心期刊
  • 主管单位:中国科学技术协会
  • 主办单位:中国病理生理学会
  • 主编:陆大祥
  • 地址:广东省广州市黄埔大道西601号
  • 邮编:510632
  • 邮箱:obsbjbb@jnu.edu.cn
  • 电话:020-85220269
  • 国际标准刊号:ISSN:1000-4718
  • 国内统一刊号:ISSN:44-1187/R
  • 邮发代号:46-98
  • 获奖情况:
  • 1997-2000年连续获得中国科协优秀基础性和高科技...,1992、1996、2000、2004、2008年,连续五次入选中...,2008-2010年,连续三年荣获“百种中国杰出学术期...,2010年获广东省期刊最高奖——品牌期刊奖
  • 国内外数据库收录:
  • 美国化学文摘(网络版),日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:37010