二烯丙三硫对乳腺癌MDA-MB-231细胞增殖和侵袭的抑制及对uPA系统的调节  

Diallyl trisulfide inhibits proliferation and invasion of breast cancer MDA-MB-231 cells and its role in regulation of uPA system

作　　者：张晶[1] 王春妮[2] 戚美[2] 王妍[3] 刘龙[3] 韩博[2,3] 

机构地区：[1]山东大学附属省立医院药剂科,济南250021 [2]山东大学医学院病理学教研室,济南250012 [3]山东大学齐鲁医院病理科,济南250012

出　　处：《山东大学学报（医学版）》2012年第10期61-67,共7页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81171951)

摘　　要：目的研究二烯丙三硫(DATS)对乳腺癌MDA-MB-231细胞增殖和侵袭能力的影响及对尿激酶型纤溶酶激活物(uPA)系统的调节作用。方法实时定量PCR法(real-time PCR)检测乳腺癌细胞株uPA系统中uPA、uPA受体(uPAR)和uPA抑制物(PAI-1)的表达;使用不同浓度DATS处理乳腺癌细胞,MTS比色法测定细胞的增殖能力;Matrigel体外浸润实验检测DATS(20～60μmol/L)对细胞浸润能力的影响;Transwell小室迁移实验和划痕试验评价60μmol/L DATS对细胞迁移能力的影响;RT-PCR和Western blot分别测定60μmol/L DATS作用后,乳腺癌细胞中uPA、uPAR和PAI-1 mRNA和蛋白表达的变化;ELISA法检测细胞培养液中PAI-1蛋白含量的变化。结果 20～80μmol/L DATS对高侵袭性乳腺癌细胞株MDA-MB-231的生长有明显的抑制作用,且呈浓度和时间依赖性。60μmol/L DATS明显抑制MDA-MB-231细胞的浸润和迁移能力,并在mRNA和蛋白水平上,显著上调PAI-1的表达,但对uPA和uPAR的表达水平无显著影响。结论 DATS抑制MDA-MB-231细胞的增殖和侵袭能力,并在mRNA和蛋白水平上,显著上调PAI-1的表达。Objective To investigate the effects of diallyl trisulfide （DATS） on proliferation and invasion of breast cancer MDA-MB-231 cells and the role for DATS in regulation of urokinase plasminogen activator （uPA） system molecules. Methods Real-time PCR was used to detect mRNA expressions of uPA, uPA receptor （uPAR） and uPA inhib- itor-1 （PAI-1） in breast cancer cell lines. MDA-MB-231 cells were treated with various concentrations of DATS, fol- lowed by MTS assay to determine cellular proliferation. Martrigel invasion assays were performed to determine invasive capacity of cancer cells after 20-60 ixmol/L DATS treatments. Transwell motility assay and healing assay were utilized to detect the effect of 60 ixmol/L DATS on migration of MDA-MB-231 ceils. Real time -PCR and western blot were used to detect mRNA and protein expressions of nPA, uPAR and PAI-1 in tumor cells. Concentrations of PAI-1 protein were determined by ELISA assay in conditioned medium with DATS treatment. Results 20-80 μmol/L DATS signifi- cantly inhibited proliferation of highly invasive breast cancer MDA-MB-231 cells in a dose- and time-dependent manner. 60μmol/L DATS inhibited invasiveness and motility capacity of MDA-MB-231 cells. PAI-1 expression was significantlyincreased by 60 ixmoL/L DATS at mRNA and protein levels, whereas uPA and uPAR expressions were not. Conclusion DATS significantly inhibits proliferation and invasion of MDA-MB-231 cell line and up-regulates PAI-1 expression at mRNA and protein levels.

关 键 词：二烯丙三硫 乳腺肿瘤 MDA—MB-231 尿激酶型纤溶酶原激活物 I型纤溶酶原激活物抑制剂 

分 类 号：R966[医药卫生—药理学] R979.1[医药卫生—药学]