CXCL12/CXCR4/MMP-2信号通路对三阴型乳腺癌生物学行为的影响  

Effect of CXCL12/CXCR4/MMP-2 signaling pathway on biological behavior in triple negative breast cancer

作　　者：焦娟[1] 宋艳艳 刘霞[1] 刘倩 冯志寅 苏丽萍[1] 何鼎盛 张巍[1] 

机构地区：[1]新疆医科大学第一附属医院病理科,乌鲁木齐830054 [2]山东省聊城市第二人民医院病理科,聊城251000 [3]新疆医科大学公共卫生学院,乌鲁木齐830054

出　　处：《临床与实验病理学杂志》2017年第11期1203-1208,共6页Chinese Journal of Clinical and Experimental Pathology

基　　金：新疆维吾尔自治区自然科学基金(2014211C049)

摘　　要：目的探讨CXCL12/CXCR4/MMP-2信号通路对三阴型乳腺癌增殖和迁移等生物学行为的影响。方法通过脂质体介导的瞬时转染CXCR4-siRNA和pc DNA3.1-CXCR4,提取MDA-MB-231细胞中RNA和蛋白质,分别用RT-PCR和Western blot法检测各组细胞中CXCR4、CXCL12及MMP-2的mRNA和蛋白质的表达变化,应用MTT实验和划痕实验检测转染后肿瘤细胞的增殖和迁移能力的改变。结果转染CXCR4-siRNA后实验组细胞中CXCR4 mRNA及蛋白表达减少(P<0.01),CXCL12mRNA及蛋白表达增加(P<0.01),MMP-2 mRNA及蛋白表达减少(P<0.01);MTT实验和划痕实验结果显示转染后72 h细胞的增殖能力下降,划痕愈合迟缓;转染pc DNA3.1-CXCR4后实验组细胞中CXCR4 mRNA及蛋白表达上调(P<0.01),CXCL12 mRNA及蛋白表达降低(P<0.01),MMP-2 mRNA及蛋白表达增加(P<0.01),MTT实验和划痕实验结果显示转染后72h细胞的增殖能力增加,划痕愈合加快。结论三阴型乳腺癌MDA-MB-231细胞中存在CXCL12/CXCR4/MMP-2信号通路的激活,抑制CXCR4表达可以抑制肿瘤细胞的增殖和迁移等恶性生物学行为。Purpose To investigate the effect of CXCL12/ CXCR4 and MMP-2 on the biological behavior of triple-negative breast cancer. Method CXCR4-siRNA and pcDNA3.1-CX- CR4were transient transfected of in MDA-MB-231 cell line by li- posome, RNA and protein were extracted. The mRNA and pro- tein expressions of CXCR4, CXCL12 and MMP-2 were detected by RT-PCR and Western blot respectively. And the migration and proliferation of the transfected cells were detected by Wound-healing assay and MTT assay. Result The experiment of RT-PCR and Westen blot demonstrated that CXCR4 mRNA and protein level expression declines after the expression CXCR4 was down-regulated （ P 〈 0. 01 ） , CXCL12 mRNA and protein level expression increased and MMP-2 mRNA and protein level expression increased after the expression CXCR4 was down-regu- lated （P 〈0. 01 ）, MTT assay and Wound-healing assay results showed that the proliferation ability of 72 h cells was decreased,and the wound healing was slow. The experiment of RT-PCR and Westen blot demonstrated that CXCR4 mRNA and protein level expression increased after the expression CXCR4 was up-regula- ted （P 〈0. 01）. The CXCL12 mRNA and protein level expres- sion declined and MMP-2 mRNA and protein level expression in- creased after the expression CXCR4 was up-regulated （P 〈 0. 01 ）, MTT assay and wound-healing assay results showed that the proliferation ability of 72 h cells was increased, and the wound healing was accelerated. Conclusion CXCL12/CX- CR4/ MMP-2 signaling pathway is activated in the triple-nega- tive breast cancer MDA-MB-231 ceils, and the inhibition of CX- CR4 can reverse the proliferation and migration of malignant bio- logical process.

关 键 词：乳腺肿瘤 三阴型乳腺癌 CXCR4 CXCL12 MMP-2 

分 类 号：R737.9[医药卫生—肿瘤]