Paeonol reverses paclitaxel resistance in human breast cancer cells by regulating the expression of transgelin 2
Paeonol reverses paclitaxel resistance in human breast cancer cells by regulating the expression of transgelin 2
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DOI：
10.1016/j.phymed.2014.02.012
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发表时间：
2014-06-15
期刊：
影响因子：
7.9
通讯作者：
Dong, Yalin
中科院分区：
文献类型：
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作者：
Cai, Jiangxia;Chen, Siying;Dong, Yalin
紫杉醇(PTX)是一种一线抗肿瘤药物，常用于乳腺癌的临床化疗。然而，化疗中耐药现象的发生极大地限制了其应用。因此，迫切需要找到逆转乳腺癌紫杉醇化疗耐药性的方法。植物衍生药物在预防致癌过程的发生和提高主流抗肿瘤药物的疗效方面具有巨大的潜力。丹皮酚是从牡丹根皮中提取的一种主要化合物，具有多种生物活性，并有逆转耐药作用的报道。本研究建立了紫杉醇耐药人乳腺癌细胞株(MCF-7/PTX)，应用双荧光素酶报告基因检测、MIT检测、流式细胞术、转染实验、Western blotting和实时定量聚合酶链式反应(qRT-PCR)研究丹皮酚的逆转作用及其机制。研究发现，转明胶2可能通过上调三磷酸腺苷结合盒转运蛋白P-糖蛋白(P-gp)、多药耐药相关蛋白1(MRP1)和乳腺癌耐药蛋白(BCRP)的表达来介导MCF-7/PTX细胞对紫杉醇的耐药。此外，丹皮酚逆转乳腺癌紫杉醇耐药的能力得到证实，逆转指数为8.2倍。此外，本研究还发现丹皮酚通过减少MCF-7/PTX细胞中P-gp、MRP1和BCRP的表达而下调转明胶2介导的紫杉醇耐药。这些结果不仅为丹皮酚在逆转紫杉醇耐药中的潜在应用提供了洞察，从而促进了乳腺癌化疗的敏感性，而且也突显了转明胶2在乳腺癌紫杉醇耐药中的潜在作用。(C)2014年爱思唯尔股份有限公司。版权所有。
Paclitaxel (PTX) is a first-line antineoplastic drug that is commonly used in clinical chemotherapy for breast cancer treatment. However, the occurrence of drug resistance in chemotherapeutic treatment has greatly restricted its use. There is thus an urgent need to find ways of reversing paclitaxel chemotherapy resistance in breast cancer. Plant-derived agents have great potential in preventing the onset of the carcinogenic process and enhancing the efficacy of mainstream antitumor drugs. Paeonol, a main compound derived from the root bark of Paeonia suffruticosa, has various biological activities, and is reported to have reversal drug resistance effects. This study established a paclitaxel-resistant human breast cancer cell line (MCF-7/PTX) and applied the dual-luciferase reporter gene assay, MIT assay, flow cytometry, transfection assay, Western blotting and the quantitative real-time polymerase chain reaction (qRT-PCR) to investigate the reversing effects of paeonol and its underlying mechanisms. It was found that transgelin 2 may mediate the resistance of MCF-7/PTX cells to paclitaxel by up-regulating the expressions of the adenosine-triphosphate binding cassette transporter proteins, including P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1), and breast cancer resistance protein (BCRP). Furthermore, the ability of paeonol to reverse paclitaxel resistance in breast cancer was confirmed, with a superior 8.2-fold reversal index. In addition, this study found that paeonol down-regulated the transgelin 2-mediated paclitaxel resistance by reducing the expressions of P-gp, MRP1, and BCRP in MCF-7/PTX cells. These results not only provide insight into the potential application of paeonol to the reversal of paclitaxel resistance, thus facilitating the sensitivity of breast cancer chemotherapy, but also highlight a potential role of transgelin 2 in the development of paclitaxel resistance in breast cancer. (C) 2014 Elsevier GmbH. All rights reserved.