葡萄糖转运蛋白1抑制剂在结肠癌细胞奥沙利铂耐药中的作用

Role of glucose transporter type 1 inhibitor in oxaliplatin resistance in colon cancer cells

目的探讨葡萄糖转运蛋白1(GLUT-1)抑制剂在结肠癌细胞奥沙利铂耐药中的作用。方法将HT29细胞分为L-OHP敏感组及耐药组,其中敏感组分为0μM、4μM、8μM、16μM、32μM、64μM L-OHP组,耐药组分为0μM、16μM、32μM、64μM L-OHP组。采用实时聚合酶链反应(PCR)和蛋白质印迹法测定耐药及敏感结肠癌细胞系葡萄糖转运蛋白-1(GLUT-1)基因表达水平。用MTT法测定耐药及敏感结肠癌细胞系细胞活力。结果低毒浓度的L-OHP处理可诱导结肠癌细胞系GLUT-1表达。与L-OHP敏感细胞系细胞相比,L-OHP耐药细胞系细胞GLUT-1表达上调。WZB117对GLUT1的抑制显著提高了L-OHP耐药细胞对药物的敏感性。结论结肠癌细胞对L-OHP的耐药可能与GLUT1表达上调有关。GLUT1特异性抑制剂可以逆转结肠癌细胞对L-OHP的抵抗。GLUT1可能是未来抗癌药物发展的一个潜在目标。

Objective To investigate the role of glucose transporter 1(GLUT-1)inhibitor in oxaliplatin resistance in colon cancer cell.Methods HT29 cells were divided into L-OHP sensitive group and L-OHP resistance group,among which the sensitive components were 0μM,4μM,8μM,16μM,32μM,64μM L-OHP group,and the resistance components were 0μM,16μM,32μM,64μM L-OHP group.Real-time polymerase chain reaction(PCR)and Western blot were used to determine the expression level of glucose transporter-1(GLUT-1)gene in drug-resistant and sensitive colon cancer cells.The cell viability of drug-resistant and sensitive colon cancer cell lines was determined by MTT method.Results L-OHP treatment with low toxic concentration can induce the expression of colon cancer cell line GLUT-1.Compared with that of L-OHP sensitive cell line cells,the expression of GLUT-1 in L-OHP resistant cell line cells was up-regulated.The inhibition of GLUT1 by WZB117 significantly increased the sensitivity of L-OHP resistant cells to drugs.Conclusion The resistance of colon cancer cells to L-OHP may be related to the up-regulation of GLUT1 expression.GLUT1 specific inhibitors can reverse the resistance of colon cancer cells to L-OHP.GLUT1 may be a potential target for the development of anticancer drugs in the future.