Resveratrol enhances the cytotoxic profile of docetaxel and doxorubicin in solid tumour cell lines in vitro
Resveratrol enhances the cytotoxic profile of docetaxel and doxorubicin in solid tumour cell lines in vitro
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DOI：
10.1111/j.1365-2184.2011.00783.x
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发表时间：
2011-12-01
影响因子：
8.5
通讯作者：
El-Shemy, H. A.
中科院分区：
文献类型：
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作者：
Al-Abd, A. M.;Mahmoud, A. M.;El-Shemy, H. A.
目的：白藜芦醇具有强大的抗氧化活性，经常被认为可能具有预防癌症的活性，最近的一些报告表明，它对几种类型的肿瘤具有癌症治疗潜力。已经发现它可以阻断P-糖蛋白并防止几种化疗药物的副作用。在这项研究中，我们评估了白藜芦醇与多西他赛和阿霉素的相互作用特征，并进一步研究了三种不同实体瘤细胞系中这种相互作用的分子基础（MCF-7、HeLa和HepG 2）。白藜芦醇本身被发现具有抗癌特性，但在所有测试的细胞系中具有相对低的效力（IC 50范围为35.1至83.8 μ M）。多柔比星和多西他赛的IC 50分别为0.48 - 0.72 μ M和25.9 - 77.8 nM。白藜芦醇与多柔比星和多西他赛的组合显着增加两种化疗药物的效力，显示IC 50范围分别为0.12至0.34 μ M和7.2至53.02 nM。联合指数显示白藜芦醇与多柔比星或多西他赛对MCF-7细胞的协同作用，以及对HeLa和HepG 2细胞的相加作用。真实的时间PCR显示，Bax和Bcl-2的表达在所有测试的细胞系中同时升高，而p53在MCF-7和HepG 2细胞中表现出边缘升高。此外，P-糖蛋白外排活性被显著抑制，随后P-糖蛋白底物在细胞内室中积累。多药耐药基因mdr 1的表达水平下调后，白藜芦醇联合阿霉素或多西他赛在所有测试cells.Conclusion：白藜芦醇增强细胞毒性的性质，这两种癌症药物在研究中使用，通过增加其细胞内水平，由于p-糖蛋白抑制和下调mdr 1基因。
Objectives: Resveratrol, with its robust antioxidant activity, has frequently been suggested as potentially having activity in cancer prevention and some recent reports have indicated that it has cancer treatment potential for several types of neoplasia. It has been found to block p-glycoprotein and to protect against several chemotherapeutic agents' side effects. In this study, we assessed interactive characteristics of resveratrol with docetaxel and doxorubicin and further investigated molecular bases of this interaction in cells of three different solid tumour lines (MCF-7, HeLa and HepG2).Materials and methods and results: Resveratrol per se was found to have anti-cancer properties, but with relatively low potency in all tested cell lines (IC50 ranged from 35.1 to 83.8 mu M). Doxorubicin and docetaxel showed IC50 ranging from 0.48 to 0.72 mu M and from 25.9 to 77.8 nM, respectively. Resveratrol in combination with doxorubicin and docetaxel significantly increased potencies of both chemotherapeutic agents showing IC50 ranging from 0.12 to 0.34 mu M and from 7.2 to 53.02 nM, respectively. The combination index showed synergistic interaction between resveratrol and doxorubicin or docetaxel on MCF-7 cells, and additive interactions on HeLa and HepG2 cells. Real time PCR revealed that expression of Bax and Bcl-2 was simultaneously elevated on combination of resveratrol with doxorubicin or docetaxel in all tested cell lines, whereas p53 exhibited marginal elevation in MCF-7 and HepG2 cells. In addition, p-glycoprotein efflux activity was significantly inhibited, with subsequent accumulation of p-glycoprotein substrate in intracellular compartments. Expression level of mdr1 gene was downregulated after resveratrol combined with doxorubicin or docetaxel in all tested cell lines.Conclusion: Resveratrol potentiates cytotoxic properties of both cancer drugs used in the study through increasing their intracellular level due to p-glycoprotein inhibition and downregulation of mdr1 gene.