摘要
目的:探讨SDF-1α/CXCR4轴对胰腺癌细胞迁移和侵袭能力的影响及其作用机制。方法:应用RT-qPCR检测4种胰腺癌细胞株CXCR4 mRNA的表达。Transwell实验检测外源性SDF-1α及其受体CXCR4靶向抑制剂AMD3100对胰腺癌细胞迁移和侵袭能力的影响。MTS法检测外源性SDF-1α及AMD3100对胰腺癌细胞活力的影响。Western blot法检测外源性SDF-1α及AMD3100对胰腺癌细胞上皮-间充质转化(EMT)相关标志物表达的影响。结果:(1) 4种胰腺癌细胞株均不同程度地表达CXCR4 mRNA,其中PANC-1细胞株表达量最高。(2)外源性SDF-1α可增强PANC-1细胞的迁移和侵袭能力,该作用可被AMD3100所阻断。(3)外源性SDF-1α处理PANC-1细胞72 h可增强细胞活力,该作用可被AMD3100阻断。(4)外源性SDF-1α通过上调SNAIL和TWIST促使PANC-1细胞发生EMT,该作用可被AMD3100所阻断。结论:SDF-1/CXCR4轴通过促进胰腺癌细胞发生EMT而促进肿瘤迁移和侵袭。
AIM:To investigate the role of SDF-1α/CXCR4 axis in pancreatic cancer cell migration and invasion.METHODS:The mRNA expression of CXCR4 in 4 pancreatic cancer cell lines was detected by RT-qPCR.The migration and invasion abilities of PANC-1 cells with the axis activated by exogenous SDF-1α or inhibited by CXCR4 inhibitor AMD3100 were detected by Transwell assays.The cell viability was measured by MTS assay.The protein expression of the epithelial-mesenchymal transition(EMT)-related molecules in the cells treated with exogenous SDF-1α or AMD3100 was determined by Western blot.RESULTS:All of the 4 pancreatic cancer cell lines expressed CXCR4 mRNA,while the PANC-1 cell line expressed the most.Exogenous SDF-1α promoted the migration and invasion abilities of PANC-1 cells,which was inhibited by AMD3100.The PANC-1 cells treated with exogenous SDF-1α for 72 h grew faster,while SDF-1α combined with AMD3100 made little significance to the viability of PANC-1 cells.Exogenous SDF-1α induced EMT of PANC-1 cells by up-regulating the expression of SNAIL and TWIST,and AMD3100 reversed this effect.CONCLUSION:SDF-1α/CXCR4 axis enhances the migration and invasion abilities of pancreatic cancer cells through inducing EMT.
作者
李若梦
邹金茂
李雅晴
陈少杰
练国达
陈茵婷
苏红
黄开红
LI Ruo-meng;ZOU Jin-mao;LI Ya-qing;CHEN Shao-jie;LIAN Guo-da;CHEN Yin-ting;SU Hong;HUANG Kai-hong(Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Department of Gastroenterology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2019年第2期273-279,共7页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81572396
No.81672408)
广东省医学科学技术研究基金项目(No.A2016210
No.A2018012)
中央高校基本科研业务费资助项目(No.18zxxt59)
广东省自然科学基金博士科研启动项目(No.2018A030310227)
广州市珠江科技新星专项(No.201610010078)