Paeonol reverses paclitaxel resistance in human breast cancer cells by regulating the expression of transgelin 2 |
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| Affiliation: | 1. Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, PR China;2. Department of Pharmacy, College of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, PR China;1. College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, South Korea;2. Research Center, Dong-A ST Co. Ltd, Yongin, South Korea;1. Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, 151 Malianwa North Road, 100193 Beijing, PR China;2. Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine (Peking Union Medical College), Ministry of Education, 100193 Beijing, PR China;3. Beijing Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, 100010 Beijing, PR China;1. State Key Laboratory of Natural Medicines, Research Department of Pharmacognosy, China Pharmaceutical University, Nanjing 211198, China;2. Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, China;3. Murad Research Institute for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;1. Department of Pharmacy, The Second Hospital of Shandong University, Jinan, China;2. Department of Neurology, The Second Hospital of Shandong University, Jinan, China;1. Department of Pharmacy, The Second Hospital of Shandong University, Jinan, Shandong 250033, China;2. Clinical laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, China;3. Institute of Clinical Pharmacology, The Second Hospital of Shandong University, Jinan, Shandong 250033, China;4. Department of Pharmacy, People''s Hospital of Zhangqiu, Jinan, Shandong 250200, China;5. Institute of Clinical Pharmacology, Qi Lu Hospital of Shandong University, Jinan, Shandong 250012, China |
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| Abstract: | 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. |
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| Keywords: | Breast cancer Paclitaxel resistance Paeonol Reverse Transgelin 2 |
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