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Characterization of multidrug‑resistant osteosarcoma sublines and the molecular mechanisms of resistance
- Source :
- Molecular medicine reports. 14(4)
- Publication Year :
- 2015
-
Abstract
- Multidrug resistance (MDR) is a challenge for the treatment of cancer and the underlying molecular mechanisms remain elusive. The current study exposed MG63 osteosarcoma cells to increasing concentrations of vincristine (VCR) to establish four VCR‑resistant MG63/VCR cell sublines (MG63/VCR1, 2, 3 and 4). The drug resistance indices (RI) of these sublines was detected with the CCK‑8 assay and determined to be163, 476, 1,247, and 2,707‑fold higher than that of parental cells, respectively. These sublines also exhibited cross‑resistance to doxorubicin, paclitaxel and pirarubicin. With increased RI, the proliferative capacity of these sublines was gradually reduced and cell morphology was also altered, characterized by increased formation of pseudopodia and long cytoplasmic processes at opposite poles. However, the migration capacity and expression of certain drug resistance‑associated genes were not in accordance with the increased RI; multidrug resistance protein 1 (MDR1) expression was significantly increased in these sublines compared with parental cells. However, in the highly resistant MG63/VCR3 and MG63/VCR4 cells, MDR‑associated protein 1, topoisomerase II and LIM domain kinase 1 levels were significantly reduced compared with the moderately resistant MG63/VCR2 cells. Expression of glutathione S‑transferase‑π mRNA was determined using reverse transcription‑quantitative polymerase chain reaction and determined that it was not changed between MG63 and MG63/VCR cells. The data of the present study demonstrated that the molecular alterations of drug resistance may change with the degree of drug resistance. Taking cell morphology into consideration, the intratumor clonal and phenotypic heterogeneity may be responsible for drug resistance. These MG63/VCR sublines may be a valuable tool to assess drug resistance and the underlying mechanisms, and to identify novel drug resistance‑associated genes or strategies to overcome MDR in human osteosarcoma.
- Subjects :
- 0301 basic medicine
Cancer Research
Cell
Antineoplastic Agents
Bone Neoplasms
Drug resistance
Cell morphology
Biochemistry
Bone and Bones
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Genetics
medicine
Humans
ATP Binding Cassette Transporter, Subfamily B, Member 1
Molecular Biology
P-glycoprotein
Osteosarcoma
biology
Cell cycle
Molecular medicine
Molecular biology
Drug Resistance, Multiple
Multiple drug resistance
Gene Expression Regulation, Neoplastic
030104 developmental biology
medicine.anatomical_structure
Oncology
Cell culture
Drug Resistance, Neoplasm
Vincristine
030220 oncology & carcinogenesis
biology.protein
Molecular Medicine
Subjects
Details
- ISSN :
- 17913004
- Volume :
- 14
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Molecular medicine reports
- Accession number :
- edsair.doi.dedup.....c5bfe5b9a7ecdb2d188ca972b7620ea5