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作 者:姚瑶[1,2] 吕志栋 夏菁[3] 崔茹婷 孔滨 YAO Yao;LÜ Zhidong;XIA Jing;CUI Ruting;KONG Bin(Department of Breast Disease Center,The Affiliated Hospital of Qingdao University,Qingdao 266100,China)
机构地区:[1]青岛大学附属医院乳腺病诊疗中心,山东青岛266100 [2]青岛大学医学部 [3]青岛市中心医院乳腺外一科
出 处:《青岛大学学报(医学版)》2022年第4期480-485,共6页Journal of Qingdao University(Medical Sciences)
基 金:中国博士后基金面上项目(2020M672001);山东省自然科学基金面上项目(ZR2020MH274);山东省医药卫生发展计划项目(2019WS112);青岛大学附属医院临床医学+X面上项目(X202101063)。
摘 要:目的探讨雌激素受体β(ER-β)对三阴性乳癌细胞生物学行为和白细胞介素8(IL-8)表达的影响。方法构建外源性ER-β慢病毒表达载体,转染人三阴性乳癌细胞MDA-MB-231。将细胞分为正常对照组、过表达组、阴性对照组和IL-8干预组。通过细胞增殖、细胞迁移实验及流式细胞术分别观察各组细胞增殖、迁移及凋亡的变化。采用蛋白印迹实验法检测各组细胞中ER-β、IL-8及凋亡相关蛋白Bax、Bcl-2和Cleavedcaspase-3表达。结果ER-β过表达慢病毒转染MDA-MB-231细胞后,ER-β的表达明显增加,而IL-8表达明显降低(F=31.17、60.26,P<0.05)。上调ER-β的表达明显抑制了MDA-MB-231的增殖和迁移能力,并促进凋亡率的增加(F=70.89~459.50,P<0.05),同时增加凋亡相关蛋白Bax/Bcl-2和Cleavedcaspase-3的表达(F=20.67、89.64,P<0.05)。但是外源性IL-8能够部分逆转ER-β对细胞迁移能力及凋亡的调控作用(P均<0.05),而对增殖无明显影响(P>0.05)。结论上调ER-β的表达可以抑制IL-8的表达,从而抑制三阴性乳癌细胞迁移并促进其凋亡。Objective To investigate the effect of estrogen receptor-β(ER-β)on the biological behavior and interleukin-8(IL-8)expression of triple-negative breast cancer cells.Methods A lentiviral vector overexpressing exogenous ER-βwas constructed and transfected into human triple-negative breast cancer MDA-MB-231 cells,which were divided into normal control group,overexpression group,negative control group,and IL-8 intervention group.CCK-8 assay,Transwell assay,and flow cytometry were used to observe the changes in cell proliferation,migration,and apoptosis,and Western blot was used to measure the expression of ER-β,IL-8,and the apoptosis-related proteins Bax,Bcl-2,and Cleaved caspase-3 in each group.Results After MDA-MB-231 cells were transfected with the ER-βoverexpression lentivirus,there was a significant increase in the expression of ER-βand a significant reduction in the expression of IL-8(F=31.17,60.26;P<0.05).Upregulation of ER-βexpression significantly inhibited the proliferation and migration abilities of MDA-MB-231 cells,promoted the increase in apoptosis rate(F=70.89-459.50,P<0.05),and increased the expression levels of the apoptosis-related proteins Bax/Bcl-2 and Cleaved caspase-3(F=20.67,89.64;P<0.05).However,exogenous IL-8 partially reversed the regulatory effect of ER-βon cell migration and apoptosis(all P<0.05),but with no significant effect on proliferation(P>0.05).Conclusion Upregulation of ER-βexpression can inhi-bit the expression of IL-8,thereby inhibiting the migration of triple-negative breast cancer cells and promoting their apoptosis.
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