汉防己甲素联合柔红霉素对K562／A02细胞株P21蛋白和P糖蛋白表达的影响

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；⑧DNR＋TET1．0mg/L组；④DNR＋TET2．0m8／／L组。采用Western blot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mdrl基因高表达，随着TET浓度的增加K562／A02细胞mdrl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mdrl及P—gp的表达有关，

Effect of Tetrandrine Combined with Daunorubicin on Expressions of P21 and P-gp in K562/A02 Cells

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 experimems 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.