黄连素对人耐紫杉醇去势性前列腺癌细胞活力、增殖及HMGB1表达的影响  

Effect of berberine on cell viability,proliferation,and HMGB1 expression of paclitaxel-resistant castration-resistant prostate cancer cells

作　　者：张健[1] 彭煜晖 李毅[1] 梁欣明 付文莉 张婷[1] 柏华 禹文峰[1] 吴昌学[1] 张启芳[1] ZHANG Jian;PENG Yuhui;LI Yi;LIANG Xinming;FU Wenli;ZHANG Ting;BAI Hua;YU Wenfeng;WU Changxue;ZHANG Qifang(Education Ministry Key Laboratory of Endemic and Minority Diseases&Key Laboratory of Molecular Biology of Guizhou Medical University,Guiyang 550004,Guizhou,China;Medical Laboratory Center,the Third Affiliated Hospital of Guizhou Medical University,Duyun 558000,Guizhou,China)

机构地区：[1]贵州医科大学地方病与少数民族疾病教育部重点实验室&贵州省医学分子生物学重点实验室,贵州贵阳550004 [2]贵州医科大学第三附属医院医学中心实验室,贵州都匀558000

出　　处：《贵州医科大学学报》2021年第6期632-638,共7页Journal of Guizhou Medical University

基　　金：国家自然科学基金(31960137);贵州省科技厅重点基金[黔科合基础(2016)1416]。

摘　　要：目的探讨黄连素(BBR)对去势抵抗性前列腺癌(CRPC)紫杉醇(PTX)耐药细胞活力、增殖及高迁移率族蛋白1(HMGB1)表达的影响。方法取对数生长期的PTX耐药前列腺癌细胞株DU145 R,用0、5、10、20、30及50μmol/LBBR处理,采用细胞计数试剂盒8(CCK8)分别于48和72 h评估6组DU145 R细胞的细胞活力;分别用二甲基亚砜(DMSO)、10及20μmol/L BBR处理对数生长期的DU145 R细胞,采用细胞克隆形成实验检测3组DU145 R细胞的克隆形成数;利用Oncomine数据库与人类蛋白质图谱数据库(HPA)分别分析HMGB1 mRNA及蛋白在前列腺癌和正常组织中的表达,利用TIMER2.0数据库分析HMGB1表达与前列腺癌患者生存的相关性;取对数生长期细胞DU145及DU145 R(分为0、10及20μmol/L BBR处理组),采用蛋白印迹法检测2组细胞中HMGB1蛋白表达。结果与0μmol/L BBR组相比,各浓度组DU145 R细胞的细胞活力降低(P<0.05);与DMSO组相比,5和10μmol/L BBR组DU145 R细胞的克隆形成数量减少(P<0.05);与正常组织相比,前列腺癌组织中HMGB1 mRNA及蛋白表达增加(P<0.001),且HMGB1高表达与前列腺癌患者不良预后相关(P=0.0193);与DU145组相比,DU145 R各组细胞HMGB1的表达明显增高(P<0.001);与0μmol/L BBR组相比,10和20μmol/L BBR组DU145 R细胞HMGB1蛋白表达下调(P<0.05)。结论BBR可抑制CRPC PTX耐药细胞增殖、细胞活力及HMGB1的表达。Objective To investigate the effects of berberine(BBR)on the viability,proliferation,and expression of high mobility group protein 1(HMGB1)of paclitaxel(PTX)resistant cells in castration-resistant prostate cancer(CRPC).Methods The PTX-resistant prostate cancer cell strain DU145 R in logarithmic growth phase was treated with 0,5,10,20,30,and 50μmol/L BBR,and the cell counting kit 8(CCK8)was used to evaluate cell viability of DU145 R cells at 48 and 72 h.The DU145 R cells in the logarithmic growth phase were treated with DMSO,10,and 20μmol/L BBR,respectively;the number of clone formation of the three groups of DU145 R cells was detected by the cell clone formation experiment.The differential expression of HMGB1 mRNA and protein in prostate cancer tissues and normal tissues were analyzed by Oncomine database and Human Protein Atlas Database(HPA)respectively.TIMER2.0 database was used to analyze the correlation between the expression of HMGB1 and the survival of prostate cancer patients.The logarithmic growth phase cells DU145 and DU145 R(divided into 0,10,and 20μmol/L BBR treatment groups)were used to detect the HMGB1 protein expression of both groups by Western blotting.Results The cell viability of DU145 R cells were decreased significantly in each group compared with the 0μmol/L BBR group(P<0.05).Compared with the DMSO group,the numbers of DU145 R cells colonies in the 5 and 10μmol/L BBR groups were decreased(P<0.05).Compared with normal prostate tissues,the expression levels of HMGB1 mRNA and protein were increased in prostate cancer tissues(P<0.001).Plus,HMGB1 high expression was associated with poor prognosis of patients with prostate cancer(P=0.0193).Compared with the DU145 group,the expression of HMGB1 in DU145 R group was significantly upregulated(P<0.001).Compared with the 0μmol/L BBR group,DU145 R cells of HMGB1 protein expression was significantly downregulated in 10 and 20μmol/L BBR groups(P<0.05).Conclusion BBR inhibits the proliferation,cell viability,and expression of HMGB1 in CRPC PTX-resista

关 键 词：前列腺肿瘤 前列腺癌细胞 紫杉醇 耐药 Oncomine数据库 人类蛋白质图谱 高迁移率族蛋白1 黄连素 

分 类 号：R737.25[医药卫生—肿瘤]