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隐丹参酮对白血病细胞伊马替尼敏感性和P-糖蛋白表达作用的研究

Keywords: 隐丹参酮,伊马替尼敏感性,白血病,P-糖蛋白

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Abstract:

隐丹参酮是丹参中主要的脂溶性活性化合物之一,对白血病等多种恶性肿瘤有显著的抑制作用,并可有效提高伊马替尼的化疗效果,但其发挥功能的分子机制仍未阐明。该文利用白血病细胞K562及其伊马替尼耐药株K562-R,系统研究了隐丹参酮对细胞伊马替尼的敏感性和P-糖蛋白表达的影响。利用MTT法检测隐丹参酮对伊马替尼增殖抑制功能的影响,AnnexinV-FITC/PI双标记流式细胞术检测细胞凋亡率的变化,Westernblot检测细胞凋亡调控蛋白Caspase-3,Caspase-9,PARP的活性变化情况;梯度浓度的隐丹参酮处理细胞后,Westernblot和流式细胞仪检测细胞中P-糖蛋白的表达水平变化,高效液相色谱法检测伊马替尼的胞内药物浓度的变化。结果隐丹参酮预处理后,显著增强了伊马替尼对K562和K562-R细胞的增殖抑制和凋亡诱导作用,细胞的促凋亡蛋白Caspase-3,Caspase-9,PARP的降解产物表达水平显著提高,与对照组相比有显著性差异(P<0.01)。而隐丹参酮对白血病细胞中P-糖蛋白表达和伊马替尼胞内药物积累没有影响。结果表明隐丹参酮可提高CML细胞对伊马替尼的化疗敏感性,其作用机制不依赖于对P-糖蛋白表达的抑制和胞内药物浓度的提高。

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