【摘要】 本研究旨在探讨汉防己甲素(TET)对人慢性髓系白血病(CML)急性红白血病细胞株K562/A02多药耐药的逆转作用,及其逆转耐药与细胞周期依赖性激酶抑制因子(p21)、P糖蛋白(P-gp)及其基因的关系,为TET的临床应用提供新的理论基础。K562/A02细胞实验分组为:①单用柔红霉素(DNR)对照组;②DNR+TET0.5mg/L组;③DNR+TET1.0mg/L组;④DNR+TET2.0mg/L组。采用Westernblot法检测实验各组K562/A02细胞P21的表达。采用流式细胞仪(FCM)检测实验各组细胞P-gp的表达,采用半定量PCR(RT-PCR)测定细胞MDR1基因mRNA表达水平。结果表明:K562/A02细胞中P21蛋白的表达随着TET浓度的增加而增强,P-gp蛋白的表达随着TET浓度的增加而减低。K562细胞中mdr1基因几乎无表达,K562/A02细胞中mdr1基因高表达,随着TET浓度的增加K562/A02细胞mdr1基因表达不断降低。结论:TET对K562/A02耐药具有逆转作用且呈浓度依赖性,其逆转耐药可能与其上调P21蛋白的表达、下调mdr1及P-gp的表达有关。更多还原

【Abstract】 This study was aimed to investigate the reversal effect of Tetrandrine(TET) combined with daunorubicin(DNR) on multidrug resistance(MDR) of K562/A02 cells and its relation to P21,P-gp and their genes so as to provide the new theoretic evidence for clinical use of TET.The experiments were divided into 4 groups:control group(DNR alone),combined 1 group(DNA+0.5 mg/L TET),combined 2 group(DNR+1.0 mg/L TET) and combined 3 group(DNR+2.0 mg/L TET).The expressions of P21,P-gp and mdr-1 gene in K562/A02 cells of different groups were detected by Western blot,flow cytometry and semi-quantitative PCR respectively.The results showed that the expression of P21 was enhanced along with increasing of TET concentration,the expression of P-gp was reduced along with increasing of TET concentration and expression of mdr-1 gene was almost not observed in K562 cells,but the high expression of mdr-1 gene was seen in K562/A02 cells,furthermore,the expression of mdr-1 gene in K562/A02 cells unceasingly was reduced along with increasing of TET concentration.It is concluded that the TET possesses the reversal effect on mnltiple drug resistance of K562/A02 cells with concentration dependence,the reversal effect of TET may be related to up-regulation of P21 expression and down-regulation of P-gp and mdr-1 gene expressions in K562/A02 cells.更多还原