title: The overexpression of MRP4 is related to multidrug resistance in osteosarcoma cells.
abstract: Doxorubicin (Adriamycin, ADM) is an antimitotic drug used in the treatment of a wide range of malignant tumors, including acute leukemia, lymphoma, osteosarcoma, breast cancer, and lung cancer. Multidrug resistance-associated proteins (MRPs) are members of a superfamily of ATP-binding cassette (ABC) transporters, which can transport various molecules across extra- and intra-cellular membranes. The aim of this study was to investigate whether there was a correlation between MRP4 and primary ADM resistance in osteosarcoma cells. In this paper, we chose the human osteosarcoma cell line MG63, ADM resistant cell line MG63/DOX, and the patient's primary cell GSF-0686. We checked the ADM sensitivity and cytotoxicity of all the three cells by cell proliferation assay. The intracellular drug concentrations were measured by using LC-MS/MS. We also examined MRP4 gene expression by RT-PCR and Western Blot. We found that the intracellular ADM concentration of the parent osteosarcoma cell line MG63 was higher than the ADM resistant osteosarcoma MG63/DOX cell line or the GSF-0686 cell after ADM treatment (P < 0.05). In addition, MRP4 mRNA and protein levels in ADM resistant osteosarcoma cells were higher than in MG63 cell (P < 0.05). Taking together, this work suggests that overexpression of MRP4 may confer ADM resistance in osteosarcoma cells.
authors: Zhonghui
authors: Z
authors: He
authors: Beibei
authors: B
authors: Hu
authors: Lina
authors: L
authors: Tang
authors: Shui'er
authors: S
authors: Zheng
authors: Yuanyu
authors: Y
authors: Sun
authors: Zan
authors: Z
authors: Sheng
authors: Yang
authors: Y
authors: Yao
authors: Department of Oncology, 6th People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
authors: Feng
authors: F
authors: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002853:Chromatography, Liquid; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D053719:Tandem Mass Spectrometry
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C073492:ABCC4 protein, human