丙泊酚抑制前列腺癌细胞增殖、迁移和侵袭的机制研究  

Study on Mechanism of Propofol Inhibiting Proliferation,Migration and Invasion of Prostate Cancer Cells

作　　者：赵翠党 史炯[2] 赵红雷 赵广平[2] 何平[2] ZHAO Cuidang;SHI Jiong;ZHAO Honglei;ZHAO Guangping;HE Ping(Department of Anesthesiology,Handan Eye Hospital the Third Hospital of Handan City,Handan,Hebei 056001,China;Department of Anesthesiology,Handan Central Hospital,Handan,Hebei 056001,China;Department of Anesthesiology,East Branch of the First Hospital of Handan City Handan Psychiatric Hospital,Handan,Hebei 056001,China)

机构地区：[1]邯郸市眼科医院邯郸市第三医院麻醉科,河北邯郸056001 [2]邯郸市中心医院麻醉科,河北邯郸056001 [3]邯郸市第一医院东区邯郸市精神病医院麻醉科,河北邯郸056001

出　　处：《临床误诊误治》2023年第7期59-67,共9页Clinical Misdiagnosis & Mistherapy

基　　金：河北省卫生健康委科研基金项目(20191850)。

摘　　要：目的 探究丙泊酚对前列腺癌(PCa)细胞增殖、迁移、侵袭的影响及对lncRNA转移相关肺腺癌转录本1(MALAT1)/miR-185-5p的调控作用。方法 采用不同浓度丙泊酚处理人PCa DU145细胞或丙泊酚80μmol/L处理24、48、72 h,采用CCK-8法、EdU染色、划痕实验、Transwell实验分别检测细胞活力、增殖、迁移和侵袭能力,采用qRT-PCR检测lncRNA MALAT1和miR-185-5p的表达,采用免疫印记实验检测Ki67、E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)和波形蛋白(Vimentin)的表达。丙泊酚处理同时单独或联合转染oe-MALAT1和miR-185-5p mimic检测MALAT1和miR-185-5p对细胞增殖、迁移和侵袭的影响。应用生物信息学和双荧光素酶报告实验分析MALAT1和miR-185-5p间的靶向关系。结果 ≥40μmol/L丙泊酚处理后DU145细胞活力显著降低,且80μmol/L丙泊酚处理后细胞毒性具有时间依赖性(P<0.01)。与对照组比较,丙泊酚显著抑制了细胞增殖、迁移和侵袭能力,显著下调Ki67、N-cadherin和Vimentin表达,上调E-cadherin表达(P<0.01);并显著下调细胞中MALAT1的表达,上调miR-185-5p的表达(P<0.05,P<0.01)。过表达MALAT1明显逆转了丙泊酚对DU145细胞的作用。双荧光素酶报告实验证实MALAT1靶向结合并负调控miR-185-5p的表达。与丙泊酚+oe-MALAT1+miR-NC组相比,丙泊酚+oe-MALAT1+miR-185-5p组EdU阳性细胞率、细胞迁移率明显降低,侵袭细胞数目明显减少,Ki67、N-cadherin和Vimentin表达显著下调,E-cadherin表达显著上调(P<0.01)。结论 丙泊酚可显著抑制PCa DU145细胞的增殖、迁移和侵袭能力,其作用机制与lncRNA MALAT1/miR-185-5p轴有关。Objective To investigate the effects of Propofol on the proliferation,migration and invasion of prostate cancer(PCa) cells and its regulation on lncrNA-related lung adenocarcinoma transcript 1(MALAT1)/miR-185-5p.Methods Human PCa DU145 cells were treated with different concentrations of Propofol or 80 μmol/L Propofol for 24,48 and 72 h.CCK-8 method,EdU staining,scratch test and Transwell test were used to detect cell viability,proliferation,migration and invasion ability,respectively.The expressions of lncRNA MALAT1 and miR-185-5p were detected by qRT-PCR,and the expressions of Ki67,E-cadherin,N-cadherin and Vimentin were detected by immunoblotting assay.The effects of MALAT1 and miR-185-5p on cell proliferation,migration,and invasion were detected after transfection of oe-MALAT1 and miR-185-5p mimic with Propofol.The targeting relationship between MALAT1 and miR-185-5p was analyzed by bioinformatics and dual luciferase reporting experiments.Results The viability of DU145 cells was significantly decreased after treatment with ≥40 μmol/L Propofol,and the cytotoxicity was time-dependent after treatment with 80 μmol/L Propofol(P<0.01).Compared with the control group,Propofol significantly inhibited cell proliferation,migration and invasion,significantly down-regulated the expressions of Ki67,N-cadherin and Vimentin,and up-regulated the expression of E-cadherin(P<0.01).The expression of MALAT1 was significantly down-regulated and the expression of miR-185-5p was up-regulated(P<0.05,P<0.01).Overexpression of MALAT1 significantly reversed the effect of Propofol on DU145 cells.Dual luciferase assay confirmed that MALAT1 targeted binding and negatively regulated the expression of miR-185-5p.Compared with the Propofol +oe-MALAT1+miR-NC group,the rate of EdU positive cells and cell migration rate and the number of invasive cells of the Propofol +oe-MALAT1+miR-185-5p group were significantly decreased,and the expressions of Ki67,N-cadherin and Vimentin were significantly down-regulated.E-cadherin expression was signifi

关 键 词：前列腺肿瘤 丙泊酚 MALAT1 miR-185-5p 细胞增殖 细胞运动 细胞侵袭 机制 

分 类 号：R737.25[医药卫生—肿瘤]