榭皮素对耐长春新碱U251/Vin细胞多药耐药的逆转作用

Reversal effect of quercetin on vincristine-induced multidrug resistance in U251/Vin cells in vitro

目的探讨榭皮素对耐长春新碱U251恶性胶质瘤细胞(U251/Vin)多药耐药的逆转作用及机制。方法 MTT法检测榭皮素对U251及其耐药株(U251/Vin)细胞的生长抑制率、半数抑制浓度(IC50)、逆转长春新碱耐药倍数,并绘制生长抑制率曲线,用酶联免疫吸附法测定P-糖蛋白(P-gp)、多药耐药相关蛋白(MRP)的表达。结果榭皮素对U251及U251/Vin细胞72 h的IC50分别为(3.80±0.05)、(4.50±0.08)mmol/L,两者比较无统计学差异(P>0.05);榭皮素作用后,U251/Vin细胞的IC50值由作用前的(5.435±0.063)μmol/L下降为(0.023±0.004)μmol/L(P<0.01),与不耐药的U251细胞IC50值(0.014±0.001)μmol/L接近(P>0.05)。加入榭皮素后U251/Vin细胞P-gp、MRP蛋白的IC50值比较有统计学差异(P均<0.05)。结论榭皮素可逆转U251/Vin细胞对长春新碱的耐药,并使P-gp、MRP的IC50降低,提示榭皮素是一种有效的肿瘤多药耐药逆转剂。

Objective To explore the reversal effect of quercetin on multidrug resistance of U251/Vin ceils, vincristine-resistent malignant glioma cells （U251 ceils ）, and its potential mechanisms. Methods The growth inhibition rate, the half inhibitory concentration （ IC50 ） , the multiple of reversing vineristine-resistance were detected by MTY assay, and the curve of growth inhibition rate was drawn. The expressions of glycoprotein （P-gp） and multiple drug-resistance related protein （MRP） were assayed by enzyme linked immunosorbent assay（ELISA）. Results The IC50 of quercetin on U251 and U251/Vin cells at 72 h were （ 3.80 ± 0. 05 ） mmol/L and （ 4.50 ± 0. 08 ）mmol/L, respectively, without significant difference （P 〉 0.05 ）. After reacting of quercetin, the IC50 of quercetin on U251/Vin ceils decreased significantly compared with before reacting of quercetin [ （0.023 ± 0. 004） p, mol/L vs （5. 435 ± 0.063 ） μmol/L, P 〈 0.01 ] closed to the level of IC5o of non-resistant U251 cells [ （0.014 ± 0. 001 ） p, mol/L] （P 〉 0.05 ）. The IC50 of P-gp and MRP in U251/Vin cells decreased significantly after adding quercetin （ all P 〈 0.05 ）. Conclusions Quereetin can reverse the vincristine-resistance on U251/Vin cells and down-regulate the IC50 of P-gp and MRP. Quercetin may serve an effective reversal agent against muhidrug-resistante of tumor.