PTC-596对人乳腺癌MCF-7细胞侵袭和迁移抑制作用及机制研究  

Inhibitory effect and mechanism of PTC-596 on invasion and migration of human breast cancer MCF-7 cells

作　　者：杨建林[1] 田家俊 陈倩影 张浩 吕亚丰 曹春雨[1] YANG Jian-lin;TIAN Jia-jun;CHEN Qian-ying;ZHANG Hao;Lü Ya-feng;CAO Chun-yu(Medical College of China Three Gorges University,Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy,Three Gorges 443002,Hubei Province,China)

机构地区：[1]三峡大学医学院,肿瘤微环境与免疫治疗湖北省重点实验室,湖北三峡443002

出　　处：《中国临床药理学杂志》2022年第21期2568-2571,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81372265,30772590);湖北省卫生健康科研基金资助项目(WJ2019H532);肿瘤微环境与免疫治疗湖北省重点实验室开放基金资助项目(2019KZL01,2016KZL04)。

摘　　要：目的研究靶向B细胞特异性小鼠白血病病毒插入位点1(Bmi-1)的小分子抑制剂PTC-596对人乳腺癌MCF-7细胞侵袭迁移的影响及作用机制。方法体外培养MCF-7细胞,分空白组(正常培养)和低、高浓度实验组(25,50 nmol·L^(-1) PTC-596)均培养48 h。以划痕愈合实验和Transwell法检测细胞迁移和侵袭能力,以克隆形成实验检测单克隆细胞群生长能力,以蛋白质印迹法检测Bmi-1、上皮钙黏素(E-cadherin)、神经钙黏素(N-cadherin)、波形蛋白(Vimentin)和基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)蛋白表达。结果空白组与低、高浓度实验组24 h划痕愈合能力分别为(76.32±3.64)%,(20.39±2.83)%,(1.32±2.49)%;迁移细胞数分别为407±38,122±35,41±13,侵袭细胞数分别为287±23,82±21,34±9;Bmi-1蛋白相对表达量分别为1.00±0.05,0.49±0.03,0.20±0.01;E-cadherin相对表达量分别为1.00±0.15,3.79±0.13,7.41±0.21;N-cadherin相对表达量分别为1.00±0.00,0.82±0.01,0.29±0.01;Vimentin相对表达量分别为1.00±0.01,0.75±0.01,0.31±0.01;MMP-2相对表达量分别为1.00±0.02,1.17±0.04,0.47±0.04;MMP-9相对表达量分别为1.00±0.02,0.63±0.04,0.32±0.03。低、高浓度实验组与空白组相比,差异均有统计学意义(均P<0.01)。结论Bmi-1抑制剂PTC-596能高效抑制人乳腺癌MCF-7细胞迁移和侵袭能力,机制可能与影响MCF-7细胞上皮-间质转化进程相关。Objective To investigate the effects of a novel small molecule inhibitor PTC-596 screened out by aiming at B-cellspecific moloney murine leukemia virus insection site 1(Bmi-1)on the influence of invasion and metastasis of human breast cancer MCF-7 cells and its molecular mechanism.Methods MCF-7 cells were divided into 3 groups:blank control group(normal culture),and low,high dose experimental groups(25,50 nmol·L^(-1) PTC-596).They were cultured for 48 h.The cell invasion and migration ability were detected by Transwell and Scratch healing experiment.The growth ability of monoclonal cell population were detected by plate cloning test.The protein expression levels of Bmi-1,E-cadherin,N-cadherin,Vimentin,matrix metalloproteinase-2(MMP-2)and matrix metalloproteinase-9(MMP-9)were detected by Western blot.Results The scratch healing ability at 24 h in blank control group and low,high dose experimental groups were(76.32±3.64)%,(20.39±2.83)%,(1.32±2.49)%,the number of migration cells were 407±38,122±35,41±13,the number of invasion cells were 287±23,82±21,34±9,Bmi-1 protein levels were 1.00±0.05,0.49±0.03,0.20±0.01,E-cadherin protein levels were1.00±0.15,3.79±0.13,7.41±0.21,N-cadherin protein levels were1.00±0.00,0.82±0.01,0.29±0.01,Vimentin protein levels were 1.00±0.01,0.75±0.01,0.31±0.01;MMP-2 protein levels were 1.00±0.02,1.17±0.04,0.47±0.04;MMP-9 protein levels were 1.00±0.02,0.63±0.04,0.32±0.03.Compared between blank control group and experimental groups,the differences were all significant(all P<0.01).Conclusion The novel Bmi-1 inhibitor PTC-596 can inhibit the migration and invasion of human breast cancer MCF-7 cells,and its mechanism may be related to epithelial to mesenchymal transition.

关 键 词：B细胞特异性小鼠白血病病毒插入位点1抑制剂 人乳腺癌MCF-7细胞 侵袭 迁移 

分 类 号：R979.1[医药卫生—药品]