论文部分内容阅读
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 possibility of reversing gastric cancer drug resistance by nuclear factor 2κB (NF2κB) inhibitor MG2132. Methods The gastric adenocarcinoma cell line SGC7901 and its vincristine (VCR) resistant SGC7901 / VCR were used as the research objects. The NF2κB DNA binding activity was detected by gel electrophoretic mobility shift assay. The expression of IκBαα protein was detected by ELISA. The immunocytochemistry Method to observe intracellular p65 nuclear translocation, MTT assay of cancer cell sensitivity to drugs. Results The basic activity of NF2κB and the activation of NFκκB induced by VCR were higher in SGC7901 / VCR resistant cells than in sensitive cells. Pretreatment of drug-resistant cells with NF2κB inhibitor MG2132 (2.5μmol / L) for 30min significantly inhibited VCR-induced NFκB activation, IκBαα degradation and p65 nuclear translocation. The median inhibitory concentration of VCR against drug-resistant cells and sensitive cells were 40.03mg / L and 0.26mg / L, respectively. MG2132 significantly increased the sensitivity of drug-resistant cells to VCR, and the multiple of drug resistance decreased from 154.0 to 16.5. However, Has little effect. Conclusion MG2132 can reverse the drug resistance of vincristine to gastric cancer cells to a certain extent by inhibiting the activation of NF2κB and improve the chemotherapy efficiency.