干扰MT1-MMP表达对口腔鳞癌细胞增殖、侵袭的影响  

Effects of MT1-MMP interference on the proliferation and invasive ability of oral squamous cell carcinoma

作　　者：肖涛 郝峰瑶 郑政[1] 谢狄亚 王志勇[1] XIAO Tao;HAO Fengyao;ZHENG Zheng;XIE Diya;WANG Zhiyong(Department of Oral and Maxillofacial Surgery,Nanjing Stomatological Hospital,Medical School of Nanjing University,Nanjing 210008,China)

机构地区：[1]南京大学医学院附属口腔医院·南京市口腔医院口腔颌面外科,江苏南京210008

出　　处：《口腔生物医学》2022年第3期160-164,共5页Oral Biomedicine

基　　金：江苏省重点研发计划专项资金项目(BE2018618)。

摘　　要：目的:检测膜型基质金属蛋白酶-1(MT1-MMP)在口腔鳞癌(OSCC)中的表达,探讨其对OSCC细胞增殖、侵袭的影响。方法:选取40例OSCC及癌旁组织样本,实时荧光定量PCR检测样本中MT1-MMP及上皮细胞钙黏蛋白(E-cadherin)mRNA表达。采用小干扰RNA(siRNA)靶向干扰HSC3细胞MT1-MMP基因,实验分为siControl、siMT1-MMP、siControl+转化生长因子-β1(TGF-β1)及siMT1-MMP+TGF-β1组。采用CCK-8法检测细胞增殖,Transwell实验检测细胞侵袭能力,Western blot检测MT1-MMP、E-cadherin、TGF-β信号通路相关蛋白CUTL1及Wnt5a的表达。结果:相对于癌旁组织,OSCC组织中MT1-MMP mRNA水平为高表达,E-cadherin为低表达(P<0.05);在干扰MT1-MMP表达后,HSC3细胞的增殖能力无明显变化(P>0.05);与siControl和siMT1-MMP组比较,siControl+TGF-β1组和siMT1-MMP+TGF-β1组细胞侵袭能力增强(P<0.01);与siControl+TGF-β1组比较,siMT1-MMP+TGF-β1组细胞侵袭能力减弱(P<0.01);与siControl组相比,siControl+TGF-β1组中MT1-MMP表达及TGF-β信号通路相关蛋白CUTL1及Wnt5a表达显著升高,E-cadherin表达下降(P<0.01);与siControl+TGF-β1组相比,siMT1-MMP+TGF-β1组中MT1-MMP、CUTL1及Wnt5a的蛋白表达水平有所下调,且E-cadherin蛋白表达水平升高(P<0.05)。结论:干扰MT1-MMP可能通过调节TGF-β1诱导的EMT进程抑制OSCC细胞侵袭。Objective:To detect the expression of membrane type 1 matrix metalloproteinase(MT1-MMP)in oral squamous cell carcinoma(OSCC)and its role on the proliferation and invasive ability of OSCC.Methods:RT-PCR was used to detect the expression of MT1-MMP and E-cadherin in OSCC and adjacent tissues;Small interfering RNA(siRNA)was used in targeted interference MT1-MMP gene in HSC3 cells.The experiment was divided into four groups:siControl group,siMT1-MMP group,siControl+transforming growth factorβ1(TGF-β1)group,siMT1-MMP+TGF-β1 group.CCK-8 method was used to detect cell proliferation of HSC3.Transwell assay was used to detect the invasive ability of cells.The expression of MT1-MMP,E-cadherin,TGF-βsignaling pathway related proteins(CUTL1 and Wnt5a)was detected by Western blot.Results:Compared with the adjacent tissues,higher expression of MT1-MMP and lower expression of E-cadherin was exhibited in OSCC(P<0.05);the cell proliferation of HSC3 cells did not change significantly after MT1-MMP interference(P>0.05);compared with siControl group and siMT1-MMP group,the HSC3 cell invasion number in siControl+TGF-β1 group and siMT1-MMP+TGF-β1 group was increased significantly;compared with siControl+TGF-β1 group,the HSC3 cell invasion number in siMT1-MMP+TGF-β1 group was decreased significantly(P<0.01);compared with siControl group,protein expression of MT1-MMP,CUTL1 and Wnt5a increased significantly in siControl+TGF-β1 group,while the expression of E-cadherin decreased(P<0.01);compared with siControl+TGF-β1 group,protein expression of MT1-MMP,CUTL1 and Wnt5a decreased partially in siMT1-MMP+TGF-β1 group,while the expression of E-cadherin increased significantly(P<0.05).Conclusions:MT1-MMP interference may inhibit the invasion of OSCC through regulating the EMT process induced by TGF-β1.

关 键 词：口腔鳞癌 膜型基质金属蛋白酶-1 上皮细胞钙黏蛋白 上皮间充质转化 

分 类 号：R739.85[医药卫生—肿瘤]