摘要
背景与目的:三阴性乳腺癌(triple-negative breast cancer,TNBC)由于其高侵袭和高转移特性,是目前乳腺癌中预后最差的一种亚型。大量研究表明塞来昔布(celecoxib)具有很好的抗肿瘤活性,可以抑制肿瘤生长、减少肿瘤血管发生,防止肿瘤的早期转移。为了进一步明确塞来昔布与TNBC细胞侵袭活性之间的关系,本实验研究塞来昔布作用下人TNBC细胞MDA-MB-231黏附、迁移及体外侵袭能力的变化,并初步探讨其可能的机制。方法:以不同浓度的塞来昔布(0、40、80、120μmol/L)作用MDA-MB-231细胞24 h后,采用细胞基质黏附实验检测塞来昔布对MDA-MB-231细胞黏附能力的影响;采用细胞划痕实验检测塞来昔布对MDA-MB-231细胞平面迁移能力的影响;采用Transwell侵袭小室实验检测塞来昔布对MDA-MB-231细胞体外侵袭能力的影响;RT-PCR检测塞来昔布作用前后基质金属蛋白酶(matrix metalloproteinases,MMPs)MMP-2和MMP-9 mRNA的表达情况。结果:经80、120μmol/L塞来昔布作用24 h后,MDA-MB-231细胞与基质的黏附能力分别为(50.2±7.3)%和(31.5±2.2)%,与对照组(96.8±10.9)%相比显著下降,差异具有统计学意义(P<0.05)。Transwell侵袭小室实验结果显示,经80、120μmol/L塞来昔布作用后MDA-MB-231细胞趋化运动明显减少,穿过人工基底膜的细胞较对照组显著降低(P<0.05)。划痕实验结果显示,经塞来昔布作用后MDA-MB-231细胞平面迁移到损伤区的细胞数明显减少(P<0.05)。RT-PCR结果显示,经塞来昔布作用MDA-MB-231细胞后,MMP-2和MMP-9 mRNA的表达水平显著降低(P<0.05)。结论:塞来昔布能显著地抑制MDA-MB-231细胞黏附、细胞体外的迁移和侵袭能力,该作用可能与抑制MMP-2和MMP-9 mRNA的表达有关。
Background and purpose:Triple-negative breast cancer(TNBC) is responsible for a disproportionate number of breast cancer death and has the worst outcome among all subtypes of breast cancer,TNBC has shown highly invasive and metastatic characteristics.There is growing evidence that celecoxib,a cyclooxygenase-2 selective inhibitor,has great potential to prevent early metastases by impeding the growth and suppressing angiogenesis in many kinds of human tumors.In this study,emphasis was placed on investigating the impacts of celecoxib on the adhesion,migration and invasion abilities of TNBC cell line MDA-MB-231 as well as its potential mechanism.Methods:MDA-MB-231 cells were treated with 0,40,80,120 μmol/L of celecoxib,respectively,for 24 h.The adhesion,migration and invasion abilities of cells in vitro were measured using adhesion assay,scratch assay and transwell invasion assay,respectively.Expressions of matrix metalloproteinases-2(MMP-2) and MMP-9 mRNA of the cells before and after celecoxib treatment were measured by RT-PCR.Results:The adhesion ratio of MDA-MB-231 cells treated with celecoxib at the concentration of 80 and 120 μmol/L decreased significantly in comparison with that in the control group [(50.2±7.3)%,(31.5±2.2)% vs(96.8±10.9)%,P<0.05].The invasive ability of MDA-MB-231 cells was significantly reduced by celecoxib after 24 h(P<0.05).In addition,the migratory number of MDA-MB-231 cells in the wounded area also decreased significantly after celecoxib treatment.The expression of MMP-2 and MMP-9 mRNA were both down-regulated after celecoxib treatment,and in the 80 and 120 μmol/L groups,the changes in the genes expression were most significant.Conclusion:Celecoxib can reduce the adhesion,migration and invasion abilities of MDA-MB-231 cells in vitro,which may be due to the down-regulation of MMP-2 and MMP-9.
出处
《中国癌症杂志》
CAS
CSCD
北大核心
2011年第4期266-271,共6页
China Oncology
基金
河北省科学技术研究与发展计划项目(No:10276167)
