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南京医科大学学报（自然科学版）                                  第41卷第3期
               ·344 ·                     Journal of Nanjing Medical University（Natural Sciences）   2021年3月


             ·基础研究·

              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



              周阳春 ，章      静，朱 峰
                    *
              南京医科大学附属逸夫医院普外科，江苏 南京                  211166




             ［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。
             ［关键词］ 结直肠癌；水通道蛋白3；缺氧诱导因子⁃1α；化疗耐药
             ［中图分类号］ R753.3                   ［文献标志码］ A                        ［文章编号］ 1007⁃4368（2021）03⁃344⁃05
              doi：10.7655/NYDXBNS20210306



              Mechanism of AQP3 in the chemoresistance of colorectal carcinoma mediated by hypoxic
              condition

                            *
              ZHOU Yangchun ，ZHANG Jing，ZHU Feng
              General Surgery，Sir Run Run Hospital Affiliated to Nanjing Medical University，Nanjing 211166，China


             ［Abstract］ 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.
             ［Key words］ colorectal carcinoma；aquaporin 3；hypoxia inducing factor⁃1α；chemoresistance
                                                                            ［J Nanjing Med Univ，2021，41（03）：344⁃348］





                                                                     结直肠癌（colorectal carcinoma，CRC）是我国最
             ［基 金 项 目］ 南 京 医 科 大 学 科 技 发 展 基 金 一 般 项 目
                                                                常见恶性肿瘤之一，且发病率逐年上升，居全部肿
             （NMUB2018313）
                                                                瘤第3位，死亡率列第4位，严重威胁我国人民生命
              ∗
               通信作者（Corresponding author），E⁃mail：zhouyang.chun@163.
                                                                    ［1］
              com                                               健康 。目前CRC治疗方法主要包括根治性手术治
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