核糖体合成调控因子1对乳腺癌细胞阿霉素抗性的影响  

EFFECTS OF REGULATOR OF RIBOSOME SYNTHESIS 1 ON RESISTANCE OF BREAST CANCER CELLS TO ADRIAMYCIN

作　　者：郑文祥 王军[1] 杨茜[2] 周娜[1] 侯琳[1] ZHENG Wenxiang;WANG Jun;YANG Qian;ZHOU Na;HOU Lin(Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, Qingdao 266071, China)

机构地区：[1]青岛大学基础医学院生物化学与分子生物学系,山东青岛266071 [2]青岛大学基础医学院病理系,山东青岛266071

出　　处：《精准医学杂志》2021年第4期287-290,共4页Journal of Precision Medicine

基　　金：国家自然科学基金资助项目(81472542);山东省重点研发项目(2019GSF107025)。

摘　　要：目的探讨核糖体合成调控因子1(RRS1)对乳腺癌细胞阿霉素抗性的影响。方法通过Western blot方法检测MCF-7和耐阿霉素MCF-7/ADR细胞中RRS1的表达;构建携带绿色荧光蛋白的shRRS1慢病毒和阴性对照慢病毒,分别感染MCF-7/ADR细胞(实验组与对照组),荧光显微镜下观察慢病毒转染效率,采用Wes-tern blot检测实验组和对照组细胞中RRS1的表达量,确定沉默效率;采用CCK8法检测实验组和对照组细胞对阿霉素的敏感性差异;采用流式细胞术分析实验组和对照组细胞内阿霉素累积量的差异;采用平板克隆实验、流式细胞术检测实验组和对照组细胞增殖和凋亡情况。结果MCF-7/ADR细胞中RRS1的表达量明显高于MCF-7细胞(t=13.05,P<0.05);与对照组相比,实验组细胞中RRS1蛋白表达水平明显降低,阿霉素对MCF-7/ADR细胞的IC50值明显降低,细胞内阿霉素的累积量明显升高,细胞增殖能力明显降低,凋亡率明显升高(t=2.87~122.40,P<0.05)。结论RRS1在耐阿霉素乳腺癌MCF-7/ADR细胞中高表达,沉默RRS1表达可显著抑制细胞增殖及诱导细胞凋亡,降低MCF-7/ADR细胞对阿霉素的抗性。Objective To investigate the effects of regulator of ribosome synthesis 1(RRS1)on adriamycin resistance in breast cancer cells.Methods Western blot was used to measure the expression of RRS1 in MCF-7 cells and adriamycin-resistant MCF-7/ADR cells.MCF-7/ADR cells were transfected separately with the shRRS1 lentivirus(experimental group)and the control shCtrl lentivirus(control group)expressing green fluorescent protein.Lentiviral transfection efficiency was observed under a fluorescence microscope.Western blot was performed to measure the expression of RRS1 in the experimental group and the control group to determine the silencing efficiency.Cell Counting Kit-8 assay was used to compare the sensitivity of cells to adriamycin between the two groups.Flow cytometry was applied to measure intracellular adriamycin accumulation for the two groups.Cell proli-feration and apoptosis were determined by the plate colony formation assay and flow cytometry.Results The expression of RRS1 in MCF-7/ADR cells was significantly higher than that in MCF-7 cells(t=13.05,P<0.05).Compared with the control group,the experimental group had significantly reduced expression of RRS1,a significantly decreased half-maximal inhibitory concentration of adriamycin against MCF-7/ADR cells,significantly increased accumulation of adriamycin in cells,significantly diminished cell proliferation,and a significantly increased apoptosis rate(t=2.87-122.40,P<0.05). Conclusion RRS1 is highly expressed in adriamycin-resistant MCF-7/ADR cell.Silencing the expression of RRS1 can significantly inhibit cell proliferation and induce apoptosis,and reduce the resistance of MCF-7/ADR cells to adriamycin.

关 键 词：乳腺肿瘤 核蛋白质类 RNA干扰 基因表达调控 肿瘤 细胞增殖 细胞凋亡 半数抑制浓度 MCF-7细胞 多柔比星 抗药性 肿瘤 

分 类 号：R737.9[医药卫生—肿瘤] R730.2[医药卫生—临床医学]