Cai Jiangxia, Chen Siying, Zhang Weipeng, Hu Sasa, Lu Jun, Xing Jianfeng, Dong Yalin
Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
Department of Pharmacy, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
Phytomedicine. 2014 Jun 15;21(7):984-91. doi: 10.1016/j.phymed.2014.02.012. Epub 2014 Mar 26.
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, MTT 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.
紫杉醇（PTX）是一种一线抗肿瘤药物，常用于乳腺癌治疗的临床化疗。然而，化疗过程中耐药性的出现极大地限制了其应用。因此，迫切需要找到逆转乳腺癌中紫杉醇化疗耐药性的方法。植物来源的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潜力。丹皮酚是一种从牡丹根皮中提取的主要化合物，具有多种生物活性，据报道具有逆转耐药性的作用。本研究建立了一种耐紫杉醇的人乳腺癌细胞系（MCF-7/PTX），并应用双荧光素酶报告基因检测、MTT检测、流式细胞术、转染检测、蛋白质印迹法和定量实时聚合酶链反应（qRT-PCR）来研究丹皮酚的逆转作用及其潜在机制。研究发现，转胶蛋白2可能通过上调三磷酸腺苷结合盒转运蛋白的表达来介导MCF-7/PTX细胞对紫杉醇的耐药性，这些转运蛋白包括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）。此外，证实了丹皮酚具有逆转乳腺癌中紫杉醇耐药性的能力，其逆转指数高达8.2倍。此外，本研究发现丹皮酚通过降低MCF-7/PTX细胞中P-gp、MRP1和BCRP的表达来下调转胶蛋白2介导的紫杉醇耐药性。这些结果不仅为丹皮酚在逆转紫杉醇耐药性方面的潜在应用提供了见解，从而提高乳腺癌化疗的敏感性，还突出了转胶蛋白2在乳腺癌紫杉醇耐药性发展中的潜在作用。
