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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 study the expression level of pregnane X receptor in malignant hematological cell line and to explore the drug-resistant reversal effect and its mechanism of Gambogic acid (GA) on K562 / A02 cell line. Methods: Real-time PCR was used to detect the expression of PXR in multiple hematological malignant cell lines. The proliferation of K562 / A02 cells was detected by MTT assay after 24, 36 and 48 h incubation with GA, DNR and GA + DNR respectively The expression of PXR in each experimental group was detected by Real-time PCR. The expression of PXR in each experimental group was detected by Western blot. Results: The expression level of PXR gene in K562 / A02 cell line was higher than that of the other malignant hematological malignant cells tested in this study. However, the resistance of daunorubicin to K562 / A02 cell line was significantly decreased by the addition of gambogic acid The inhibitory rate of PXR was increased in K562 / A02 cells treated with gambogic acid, but not in daunorubicin group, suggesting that daunorubicin did not down-regulate PXR effect. PXR down is not the illusion of cells after drug-killing, and gambogic acid can down-regulate PXR gene and protein expression. Conclusion: PXR can be expressed in a variety of hematological malignant tumor cell lines and is highly expressed in K562 / A02 cells compared with other experimental cell lines. Low-dose GA can increase the growth inhibition rate of cells and enhance the effect of chemotherapy, which may be related to the down-regulation of PXR expression.