槲皮素对人子宫内膜癌耐药细胞株B-MD-C1(ADR^(+/+))多药耐药基因mdr1及P-gp蛋白表达的影响

Mechanisms of Multidrug Resistance Reversal on B-MD-C1(ADR^(+/+))by Quercetin

背景与目的:探讨槲皮素对人子宫内膜癌耐药细胞株B-MD-C1(ADR+/+)多药耐药基因mdr1及P-gp蛋白表达的影响。材料与方法:经槲皮素干预B-MD-C1(ADR+/+)细胞后,RT-PCR法检测细胞多药耐药基因mdr1表达的变化;免疫组织化学法检测多药耐药蛋白P-gp表达的变化;共聚焦激光扫描显微镜检测耐药细胞及相应敏感细胞内阿霉素(ADM)的分布情况;MTT法检测槲皮素作用后B-MD-C1(ADR+/+)细胞对化疗敏感性的变化。结果:经不同浓度槲皮素干预后,B-MD-C1(ADR+/+)细胞多药耐药基因mdr1及相应蛋白P-gp表达水平下调(P<0.05);槲皮素干预后,能恢复ADM在B-MD-C1(ADR+/+)细胞内的分布,增加细胞内ADM浓度,从而逆转细胞的耐药性(P<0.05)。结论:槲皮素逆转B-MD-C1(ADR+/+)细胞多药耐药性,该作用可能与下调细胞多药耐药基因mdr1及其编码蛋白P-gp的表达有关。

BACKGROUND AND AIM：Effects of quercetin on expressions of mdr1 gene and P-glycoprotein in B-MD-C1（ADR^＋/＋） cell line were studied in vitro.MATERIALS AND METHODS：After treatment with or without various concentrations of quercetin（10,20,40 μmol/L） for 48 h,the expression in mdr1 gene in B-MD-C1（ADR^＋/＋） cell was detected by RT-PCR and expression of P-gp protein with IHC.The chemosensibility of B-MD-C1（ADR^＋/＋） cells was evaluated by means of MTT.Changes of subcellular distribution of ADM in B-MD-C1（ADR^＋/＋） cell was examined by confocal scanning laser microscopy （CSLM）. RESULTS： After treatment with different concentrations of quercetin （10, 20, 40 μmol/L） for 48 h, the expression levels of mdrl gene and P-glycoprotein in B-MD-CI（ADR^＋/＋） cells were decreased significantly（P 〈 0.05） The abnormal distribution of ADM in B-MD-CI（ADR^＋/＋） cells was restored. CONCLUSION： Quercetin could reverse the multidrug resistance by down-regulating the expression of mdr1 gene and P-glycoprotein and restoring the distribution of ADM in B-MD-C1 （ADR^＋/＋） cells.