title: Paeonol reverses paclitaxel resistance in human breast cancer cells by regulating the expression of transgelin 2.
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.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Jiangxia
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Siying
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Weipeng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Sasa
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Pharmacy, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China. Electronic address: dongyalin@mail.xjtu.edu.cn.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Dong
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000098:Acetophenones / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics; D017239:Paclitaxel / Q000009:adverse effects* / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000098:Acetophenones; D000972:Antineoplastic Agents, Phytogenic; D008840:Microfilament Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D017239:Paclitaxel; C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; C585387:Tagln2 protein, human; C013638:paeonol; C421109:multidrug resistance-associated protein 1
keywords: Breast cancer; Paclitaxel resistance; Paeonol; Reverse; Transgelin 2