SDF-1α/CXCR7介导结肠癌细胞对5-FU的耐药作用  

SDF-1α/CXCR7 mediating colon carcinoma cells resistant to 5-FU

作　　者：黄鹏 王国琴[2] 董泽涛 张旭明 刘馨[1] 黄尤光[1] 

机构地区：[1]昆明医科大学第三附属医院肿瘤研究所,云南昆明650118 [2]昆明医科大学第三附属医院姑息科,云南昆明650118 [3]昆明市第二人民医院公共卫生部,云南昆明650204

出　　处：《肿瘤》2018年第1期18-24,共7页Tumor

基　　金：云南省卫生科技计划项目(编号:2012WS0040)~~

摘　　要：目的:探讨间质细胞衍生因子1α(stromal cell-derived factor-1α,SDF-1α)通过其CXC结构趋化因子受体4(CXC-domain chemokine receptor 4,CXCR4)和CXCR7介导结肠癌细胞对5-氟尿嘧啶(5-uorouracil,5-FU)的耐药性及其可能的作用机制。方法:应用蛋白质印迹法检测结肠癌SW480、SW620、HCT116和HT29细胞中CXCR4和CXCR7的表达水平。分别用SDF-1α、SDF-1α+AMD3100(CXCR4抑制剂)或SDF-1α+抗CXCR7单克隆抗体处理SW480和HT29细胞6 h,再分别用3.1、6.25、12.5、25、50、100和150μg/mL 5-FU处理48 h后,应用磺酰罗丹明B(sulforhodamine B,SRB)染色法检测5-FU对各组细胞的半数抑制浓度(half inhibitory concentration,IC50)值,应用蛋白质印迹法检测各组结肠癌细胞中耐药相关蛋白P-糖蛋白(P-glycoprotein,P-gp)和多药耐药蛋白1(multidrug resistance protein-1,MRP-1)的表达情况。结果:结肠癌SW480和HT29细胞中CXCR4和CXCR7蛋白的表达水平高于SW620和HCT116细胞(P值均<0.05)。对于SW480和HT29细胞,SDF-1α处理组5-FU的IC50值高于未处理的对照组(P值均<0.05),SDF-1α+抗CXCR7单克隆抗体处理组5-FU的IC50值低于SDF-1α处理组(P值均<0.01),SDF-1α+AMD3100处理组5-FU的IC50值与SDF-1α处理组间的差异无统计学意义(P值均>0.05)。SW480和HT29细胞中,SDF-1α+抗CXCR7单克隆抗体处理组P-gp蛋白的表达水平均低于SDF-1α处理组(P值均<0.05),SDF-1α+AMD3100处理组P-gp蛋白的表达水平与SDF-1α处理组间的差异均无统计学意义(P值均>0.05);各组细胞中,MRP-1的表达水平间差异均无统计学意义(P值均>0.05)。结论:SDF-1α可促进结肠癌细胞对5-FU产生耐药性,这可能与SDF-1α/CXCR7信号通路上调P-gp的表达水平有关。Objective： To investigate the effects of stromal cell-derived factor-1α （SDF-1α） through CXC-domain chemokine receptor 4 （CXCR4） and CXCR7 on colonic cancer cells resistant to 5-fluorouracil （5-FU）, and to explore its possible mechanism. Methods： The expression levels of CXCR4 and CXCR7 in colonic cancer SW480, SW620, HCT116 and HT29 cells were detected by Western blotting. After treatment with SDF-1α, SDF-1α in combination with AMD3100 （CXCR4 inhibitor） or SDF-1α in combination with anti- CXCR7 monoclonal antibody for 6 hours, the SW480 and HT29 cells were then treated with 3.1, 6.25, 12.5, 25, 50, 100 and 150 μg/mL 5-FU for 48 hours. The half inhibitory concentration （IC50） value of 5-FU was detected by sulforhodamine B （SRB） assay. The expressions of drugresistant proteins P-glycoprotein （P-gp） and multidrug resistance protein-1 （MRP-1）were detected by Western blotting. Results： The expression levels of CXCR4 and CXCR7 in SW480 and HT29 cells were higher than those in SW620 and HCT116 cells （all P 〈 0.05）. The ICs0 values of 5-FU for SW480 and HT29 cells in SDF-1α group were higher than those in the control group （SW480 and HT29 cells without any treatment） （both P 〈 0.05）. The ICs0 values of 5-FU for SW480 and H-I-29 ceils in group of SDF-1α in combination with anti-CXCR7 monoclonal antibody were lower than those in SDF-1α group （both P 〈 0.01）. The ICs0 values of 5-FU for SW480 and HT29 cells had no significant differences between group of SDF-1α in combination with AMD3100 and group of SDF-1α （both P 〉 0.05）. The expression levels of P-gp in SW480 and HT29 cells in group of SDF-1α in combination with anti-CXCR7 monoclonal antibody were lower than those in SDF-1α group （both P 〈 0.05）. The expression levels of P-gp in SW480 and HT29 cells had no significant differences between group of SDF-1α in combination with AMD3100 and group of SDF-1α （both P 〉 0.05）. The expression level of MRP-1 had no significant difference a

关 键 词：结肠肿瘤 抗药性 肿瘤 多药耐药相关蛋白质类 间质细胞衍生因子1α CXC结构趋化因子受体4 

分 类 号：R735.35[医药卫生—肿瘤]