文章摘要
周阳春,章 静,朱 峰.水通道蛋白3参与缺氧介导的结直肠癌化疗耐药的机制研究[J].南京医科大学学报,2021,(3):344~348
水通道蛋白3参与缺氧介导的结直肠癌化疗耐药的机制研究
Mechanism of AQP3 in the chemoresistance of colorectal carcinoma mediated by hypoxic condition
投稿时间:2020-04-02  
DOI:10.7655/NYDXBNS20210306
中文关键词: 结直肠癌  水通道蛋白3  缺氧诱导因子⁃1α  化疗耐药
英文关键词: colorectal carcinoma  aquaporin 3  hypoxia inducing factor⁃1α  chemoresistance
基金项目:南京医科大学科技发展基金一般项目(NMUB2018313)
作者单位
周阳春 南京医科大学附属逸夫医院普外科江苏 南京 211166 
章 静 南京医科大学附属逸夫医院普外科江苏 南京 211166 
朱 峰 南京医科大学附属逸夫医院普外科江苏 南京 211166 
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中文摘要:
      目的:探讨水通道蛋白3(aquaporin 3,AQP3)在缺氧介导结直肠癌(colorectal carcinoma,CRC)化疗耐药中的作用及意义。方法:通过实时荧光定量PCR和Western blot实验检测缺氧条件下结直肠癌HCT116、HT29细胞中AQP3表达的变化;通过CCK?8实验检测在氟尿嘧啶(5?fluorouracil,5?Fu)作用下,缺氧对 HCT116细胞化疗敏感性的影响;通过CCK?8和平板克隆形成实验检测AQP3对缺氧条件下HCT116细胞化疗敏感性的影响。结果:在缺氧条件下,HCT116、HT29细胞中AQP3 mRNA以及蛋白表达水平均显著上调;抑制缺氧诱导因子?1α(hypoxia inducible factor,HIF?1α)表达,缺氧条件下HCT116细胞中AQP3 mRNA、蛋白表达水平均未显著增加。在缺氧条件下,HCT116细胞对5?Fu的化疗敏感性低于常氧条件;抑制AQP3表达,HCT116细胞对5?Fu化疗敏感性增加。平板克隆形成实验也证明了抑制AQP3表达可增加HCT116细胞在缺氧条件下的化疗敏感性。结论:在缺氧条件下,HIF?1α上调AQP3表达,继而导致结直肠癌细胞对5?Fu耐药。
英文摘要:
      Objective:This study aims to investigate the role of aquaporin 3(AQP3) in the chemoresistance of colorectal carcinoma mediated by hypoxia. Methods:Real?time quantitative PCR and Western blot were performed to detect the expression of AQP3 under hypoxic condition in colorectal carcinoma HCT116 cells and HT29 cells. CCK?8 was used to detect the influence of hypoxia on the sensitivity of HCT116 cells to 5?fluorouracil(5?Fu)under hypoxic condition. CCK?8 and colony formation assay were also used to detect the effect of AQP3 on the sensitivity of HCT116 cells to 5?Fu under hypoxic condition. Results:Under hypoxic condition,the expression levels of AQP3 mRNA and protein were significantly up?regulated in both HCT116 and HT29 cells. After hypoxia inducible factor(HIF?1α)was inhibited,and the expression levels of AQP3 mRNA and protein in HCT116 cells under hypoxic condition were not significantly increased. Under hypoxic condition,the sensitivity of HCT116 cells to 5?Fu was lower than that in normal oxygen condition,which was reversed by inhibiting AQP3. Colony formation assay also demonstrated that the effect of 5?Fu on the proliferation ability of HCT116 cells was smaller under hypoxic condition,which was reversed by inhibiting AQP3. Conclusion:Under hypoxic condition,colorectal carcinoma up?regulated AQP3 expression by HIF?1α,which lead to 5?Fu chemoresistance.
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