Direct assessment of P-glycoprotein efflux to determine tumor response to chemotherapy.
Direct assessment of P-glycoprotein efflux to determine tumor response to chemotherapy.
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DOI：
10.1016/j.bcp.2010.03.010
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发表时间：
2010-07-01
影响因子：
5.8
通讯作者：
Liu, Yong-Yu
中科院分区：
文献类型：
--
作者：
Patwardhan, Gauri;Gupta, Vineet;Huang, Juowen;Gu, Xin;Liu, Yong-Yu
多药耐药性是癌症化疗成功的主要障碍。从细胞中挤出抗癌药物的过度产生的P-糖蛋白是在多药耐药癌症中检测到的最常见机制。直接测量体内肿瘤的细胞外排，而不是估计储存或包埋样品中的MDR 1 mRNA和P-糖蛋白水平，可以在功能上表征耐药机制，并确定癌症患者抗癌药物的选择。因此，我们介绍了一种新的方法来直接测定肿瘤的P-糖蛋白流出。采用Flutax-2（俄勒冈州绿色-488紫杉醇）和荧光分光光度法，该方法已成功地测量了细胞转运性，包括在不同的癌细胞系，肿瘤和其他组织中的流出和积累，具有高重现性。用这种方法，我们已经定量测定了与P-糖蛋白水平相关的细胞外排，以及乳腺癌、卵巢癌、宫颈癌和结肠癌细胞系和荷瘤小鼠中药物的逆转作用。在约5 mg肿瘤或其他组织中，它灵敏地检测到这些P-糖蛋白流出的改变，具有高置信度。这种直接和快速的功能评估有可能确定手术切除后不同类型癌症的耐药性。该方法在临床环境中用于耐药诊断的目的需要进一步验证。
Multidrug resistance is a major impediment to the success of cancer chemotherapy. The overproduced P-glycoprotein that extrudes anticancer drugs from cells, is the most common mechanism detected in multidrug-resistant cancers. Direct measurement of cellular efflux of tumors in vivo, rather than estimation of MDR1 mRNA and P-glycoprotein levels in samples stored or embedded, can functionally characterize the mechanism of drug resistance and determine the choice of anticancer drugs for cancer patients. Herewith, we introduce a new approach to directly determine P-glycoprotein efflux of tumors. Employing Flutax-2 (Oregon green-488 paclitaxel) and fluorescence spectrophotometry, this method has successfully measured cellular transportability including efflux and accumulation in diverse cancer cell lines, tumors and other tissues with high reproducibility. With this method, we have quantitatively determined cellular efflux that is correlated with P-glycoprotein levels and the reversal effects of agents in cell lines of breast, ovarian, cervical and colon cancers, and in tumor-bearing mice. It has sensitively detected these alterations of P-glycoprotein efflux in approximately 5 mg tumor or other tissues with high confidence. This direct and quick functional assessment has a potential to determine drug resistance in different types of cancers after surgical resection. Further validation of this method in clinic settings for the diagnosis of drug resistance purpose is needed.
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肿瘤细胞中P-糖蛋白相关的多药耐药性定量评估的一种新方法。
影响因子：
8.8
作者：
Homolya, L;Hollo, M;Muller, M;Mechetner, E B;Sarkadi, B
通讯作者：
Sarkadi, B
影响因子：
6.4
作者：
LAI, GM;CHEN, YN;BATES, SE
通讯作者：
BATES, SE
影响因子：
45.3
作者：
Claret, Laurent;Girard, Pascal;Bruno, Rene
通讯作者：
Bruno, Rene
影响因子：
10.3
作者：
KERN, DH;WEISENTHAL, LM
通讯作者：
WEISENTHAL, LM
影响因子：
8.8
作者：
Kramer, R;Weber, T K;Arceci, R;Ramchurren, N;Kastrinakis, W V;Steele, G Jr;Summerhayes, I C
通讯作者：
Summerhayes, I C