| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Cai, Jiangxia Chen, Siying Zhang, Weipeng Hu, Sasa Lu, Jun Xing, Jianfeng Dong, Yalin |
| Description |
Author Affiliation: Cai J ( Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.); Chen S ( Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.); Zhang W ( Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.); Hu S ( Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.); Lu J ( Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.); Xing J ( Department of Pharmacy, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.); Dong Y ( 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.) |
| 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. |
| File Format |
HTM / HTML |
| ISSN |
09447113 |
| Issue Number |
7 |
| Volume Number |
21 |
| e-ISSN |
1618095X |
| Journal |
Phytomedicine |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2014-06-15 |
| Publisher Place |
Germany |
| Access Restriction |
One Nation One Subscription (ONOS) |
| Subject Keyword |
Discipline Complementary Therapies Acetophenones Pharmacology Breast Neoplasms Drug Therapy Drug Resistance, Neoplasm Drug Effects Microfilament Proteins Genetics Muscle Proteins Paclitaxel Adverse Effects Atp-binding Cassette Transporters Antineoplastic Agents, Phytogenic Pathology Female Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Humans Mcf-7 Cells Metabolism Multidrug Resistance-associated Proteins Neoplasm Proteins P-glycoproteins Promoter Regions, Genetic Up-regulation Journal Article Research Support, Non-u.s. Gov't |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Drug Discovery Molecular Medicine Pharmacology Complementary and Alternative Medicine Pharmaceutical Science |
