藤黄酸联合柔红霉素对白血病耐药细胞株K562/A02孕烷X受体表达的影响（英文）

Effects of Garcinia Acid Combined with Daunorubicin on Expression of Pregnane X Receptor in Leukemia Cell Line K562/ A02

目的:研究恶性血液病细胞株孕烷X受体(Pregnane X receptor)的表达水平;探讨藤黄酸(Gambogic acid,GA)对K562/A02耐药细胞株的耐药逆转作用及其机制。方法:应用Real-time PCR法检测多个恶性血液病细胞株中PXR的表达;采用MTT法检测K562/A02细胞株分别与GA,DNR,GA+DNR孵育24、36、48 h后的细胞增殖抑制率;Real-time PCR法检测各实验组PXR表达;Western blot法检测各实验组细胞PXR蛋白的表达水平。结果:K562/A02细胞株的PXR基因表达水平高于本研究实验其他所检测的恶性血液病细胞;经藤黄酸作用后,K562/A02细胞对柔红霉素的耐药性明显降低,却细胞抑制率增加;藤黄酸作用后的K562/A02细胞的PXR基因和蛋白表达水平均较对照组下调,而在柔红霉素组则无明显变化,提示柔红霉素并没有下调PXR的作用。PXR的下调亦不是细胞被药物杀伤后的假象,而藤黄酸可以下调PXR的基因和蛋白表达。结论:PXR可在多种血液系统恶性肿瘤细胞株中表达,并在K562/A02细胞明显较其他实验细胞株中表达高。低剂量GA可以提高细胞的生长抑制率,增强化疗的效果,其机制可能与下调PXR表达有关。

Objective: To explore the expression of PXR( Pregnane X receptor) in several malignant hematological cell lines,and to investigate the reversal effect of Gambogic acid( GA) on multi-drug resistance( M DR) of K562 / A02 cell line and its reversal mechanism. Methods: Transcription of PXR was detected by real-time PCR in several malignant hematological cell lines. The growth inhibition rate of K562 / A02 in different experimental groups was assayed by M TT method,and the expression of PXR protein was measured by Western blot. Results: PXR gene transcription could be detected in several hematological malignancy cell lines,and it was significantly higher in K562 / A02 cell line,compared with the other cell lines used in this experiment. Low-dose GA could enhance cell growth inhibition rate,increasing the effect of chemotherapy,which may be associated with down-regulation of PXR expression. PXR gene transcription and protein expression in GA and DNR + GA groups decreased as compared with control group and the DNR group,suggesting that low-dose GA can down-regulate PXR gene transcription and protein expression. Conclusion: PXR gene transcription can be detected in several hematological malignancy cell line,which is significantly higher in K562 / A02 cell line,as compared with the other cell lines used in this experiment. Low-dose GA can enhance cell growth inhibition rate,increasing the effect of chemotherapy,which may be associated with down-regulation of PXR expression.