核因子-κB抑制剂逆转人胃癌细胞对长春新碱耐药性的研究  

Reversal of chemoresistance to vincristine in gastric cancer cells by NF κB inhibitor

作　　者：王维[1] 罗和生[1] 

机构地区：[1]武汉大学人民医院消化内科

出　　处：《中华肿瘤杂志》2005年第6期335-338,共4页Chinese Journal of Oncology

摘　　要：目的研究核因子2κB(NF2κB)抑制剂MG2132逆转胃癌耐药的可能性。方法以胃腺癌细胞株SGC7901及其长春新碱(VCR)耐药株SGC7901/VCR为研究对象,通过凝胶电泳迁移率分析检测NF2κBDNA结合活性,ELISA法检测细胞内IκB2α蛋白的表达,免疫细胞化学法观测细胞内p65核转位,MTT法检测癌细胞对药物的敏感性。结果SGC7901/VCR耐药细胞中,NF2κB的基础活性及不同浓度VCR诱导的NF2κB活化程度均比敏感细胞高。NF2κB抑制剂MG2132(2.5μmol/L)预处理耐药细胞30min,可明显抑制VCR诱导的NF2κB活化、IκB2α降解和p65核转位。VCR对耐药细胞和敏感细胞的半数抑制浓度分别为40.03mg/L和0.26mg/L,MG2132可显著提高耐药细胞对VCR的敏感性,耐药倍数由154.0降至16.5,但对敏感细胞影响不大。结论MG2132可通过抑制NF2κB的活化,在一定程度上逆转胃癌细胞对长春新碱的耐药性,提高化疗效率。Objective To investigate the reversing effect of NF κB inhibitor MG 132 on chemoresistance of gastric cancer cells to vincristine. Methods In vincristine resistant human gastric cancer cells (SGC7901/VCR) and the parental sensitive clone (SGC7901), NF κB DNA binding activity was determined by electrophoreses mobility shift assay (EMSA). The inhibition level of κB (IκB α) expression was measured by cellular ELISA. Immunocytochemistry was used to detect the translocation of p65 and chemosensitivity of the cells was determined by MTT assay. Results Compared with the parental SGC7901 cells, both the baseline and VCR induced NF κB DNA binding activities in various concentrations were all higher in the SGC7901/VCR cells. Pretreatment with MG 132, the NF κB inhibitor, for 30 minutes remarkably reduced the NF κB activation, IκB α degradation and nuclear translocation of p65. As to the SGC7901/VCR cells and the parental sensitive SGC7901 cells, the IC 50 values for VCR were 40.03 mg/L and 0.26 mg/L, respectively. MG 132 (2.5 μmol/L) significantly enhanced the toxicity of VCR in SGC7901/VCR cells and decreased the resistance index from 154.0 to 16.5. However, MG 132 did not show an obvious effect on the VCR sensitivity in sensitive SGC7901 cells. Conclusion Our data indicate that inhibition of NF κB activation in gastric cancer cells may reverse the drug resistance to VCR in the cancer cells and increase the efficiency of chemotherapy.

关 键 词：核因子-KB 胃癌细胞 长春新碱 耐药性 

分 类 号：R735.2[医药卫生—肿瘤]