SDF-1α/CXCR4轴通过诱导胰腺癌上皮-间充质转化促进肿瘤迁移和侵袭

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-1αor 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-1αor 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-1αpromoted the migration and invasion abilities of PANC-1 cells, which was inhibited by AMD3100.The PANC-1 cells treated with exogenous SDF-1αfor 72 h grew faster, while SDF-1αcombined with AMD3100 made little significance to the viability of PANC-1 cells.Exogenous SDF-1αinduced 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.