黄芩苷对白血病细胞耐药株逆转耐药效果及机制研究

Reversal effect and machenism induced by baicalin on leukemia cell line

目的:观察黄芩苷对白血病耐药株细胞的耐药逆转作用,并初步探讨其可能的机制。方法:MTT法检测阿霉素及黄芩苷对白血病亲本细胞及耐药株细胞的抑制率,通过计算阿霉素对耐药株细胞及亲本细胞的半数抑制浓度(IC50)评价耐药倍数,通过阿霉素与黄芩苷联用的IC50评价黄芩苷的逆转作用,流式细胞计数法检测黄芩苷作用后对耐药细胞内阿霉素药物蓄积的影响,RT-PCR检测黄芩苷对耐药细胞中多药耐药相关基因MDR1、MRP1以及LRP1表达的影响。结果:耐药细胞株的耐药倍数为17.384倍,黄芩苷10μg/ml和20μg/ml对白血病耐药株的逆转倍数分别为4.230和7.812,相对逆转率分别为0.81和0.93,黄芩苷作用后耐药株细胞内阿霉素蓄积明显增加,MDR1基因表达显著下降。结论:黄芩苷对白血病耐药细胞株具有显著的逆转作用,其机制可能与下调了细胞内的MDR1基因表达进而抑制P糖蛋白对阿霉素的泵出有关。

Objective： To observe reversal effect of baicalin on the leukemia cells,and to explore its possible mechanism.Methods： The inhibition rates of adriamycin and baicalin on parental cells or drug-resistant leukemia cells were determined by MTT assay,evaluation of multiple drug resistance and the reversal effect of baicalin was calculated according to half inhibitory concentration（IC50） of adriamycin on adriamycin-resistant cell lines and parental cells,effect of baicalin on drug accumulation of adriamycin in drug-resistant cells was analysed by flow cytometry assay,RT-PCR detection was executed to investigate MDR1,MRP1 and LRP1 expression in the resistant cells after treatment of baicalin.Results： The Resistance Index of drug-resistant cell lines was 17.384,the reverse rate of baicalin with 10μg/ml and 20μg/ml were 4.230 and 7.812,respectively,relative reversal rate were 0.81 and 0.93,baicalin could significantly increase adriamycin accumulation and decrease the expression of MDR1 gene significantly.Conclusion： Baicalin illustrated a significant reversal effect on the leukemia cell line,the mechanism may be to reduce MDR1 gene expression in the cell to keep p-glycoprotein pumping the adriamycin out of cells.