Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells
Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells
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DOI：
10.1016/s0006-2952(02)01224-8
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发表时间：
2002-08-15
影响因子：
5.8
通讯作者：
Limtrakul, P
中科院分区：
文献类型：
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作者：
Anuchapreeda, S;Leechanachai, P;Limtrakul, P
多药耐药（MDR）是一种通常与患者肿瘤细胞中细胞内药物积累减少相关的现象，其由增强的药物外排引起。它通常与肿瘤细胞表面P-糖蛋白（Pgp）的过度表达有关，从而降低药物的细胞毒性。在这项研究中，姜黄素被测试其潜在的能力，以调节Pgp在多药耐药的人宫颈癌细胞系KB-V1的表达和功能。Western印迹分析和逆转录-聚合酶链反应（RT-PCR）显示，1，5，和10 μ M姜黄素处理长达72小时能够显着降低KB-V1细胞中的Pgp表达。姜黄素（1-10 μ M）以浓度依赖性方式降低Pgp表达，并发现对MDR 1 mRNA水平具有相同的作用。姜黄素对Pgp功能的影响通过罗丹明123（Rh 123）在Pgp表达的KB-V1细胞中的积累和流出来证明。姜黄素以浓度依赖性方式（1-55 μ M）增加Rh 123积累，并抑制Rh 123从这些细胞的流出，但不影响Rh 123从野生型药物敏感KB-3-1细胞的流出。用姜黄素处理耐药KB-V1细胞增加了它们对长春碱的敏感性，这与Rh 123的细胞内积累增加一致。此外，姜黄素以浓度依赖性方式抑制维拉帕米刺激的ATP酶活性和Pgp与哌唑嗪类似物[I-125]碘芳基齐唑嗪的光亲和标记，表明姜黄素直接与转运蛋白相互作用。因此，姜黄素似乎能够调节多药耐药人KB-V1细胞中Pgp的体外表达和功能。总之，本研究描述了植物化学物质姜黄素对MDR 1表达和Pgp功能的双重调节，这可能是一种有吸引力的癌细胞化疗增敏剂。(C)2002年爱思唯尔科技有限公司All rights reserved.
Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in the tumor cells of a patient, resulting from enhanced drug efflux. It is often related to the overexpression of P-glycoprotein (Pgp) on the surface of tumor cells, thereby reducing drug cytotoxicity. In this study, curcumin was tested for its potential ability to modulate the expression and function of Pgp in the multidrug-resistant human cervical carcinoma cell line KB-V1. Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) showed that treatment with 1, 5, and 10 muM curcumin for up to 72 hr was able to significantly lower Pgp expression in KB-V1 cells. Curcumin (1-10 muM) decreased Pgp expression in a concentration-dependent manner and was also found to have the same effect on MDR1 mRNA levels. The effect of curcumin on Pgp function was demonstrated by rhodamine 123 (Rh123) accumulation and efflux in Pgp-expressing KB-V1 cells. Curcumin increased Rh123 accumulation in a concentration-dependent manner (1-55 muM) and inhibited the efflux of Rh123 from these cells, but did not affect the efflux of Rh123 from the wild-type drug-sensitive KB-3-1 cells. Treatment of drug-resistant KB-V1 cells with curcumin increased their sensitivity to vinblastine, which was consistent with an increased intracellular accumulation of Rh123. In addition, curcumin inhibited verapamil-stimulated ATPase activity and the photoaffinity labeling of Pgp with the prazosin analog [I-125]iodoarylazidoprazosin in a concentration-dependent manner, demonstrating that curcumin interacts directly with the transporter. Thus, curcumin seems to be able to modulate the in vitro expression and function of Pgp in multidrug-resistant human KB-V1 cells. In summary, this study describes the duel modulation of MDR1 expression and Pgp function by the phytochemical curcumin, which may be an attractive new agent for the chemosensitization of cancer cells. (C) 2002 Elsevier Science Inc. All rights reserved.