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Article

Characterization of multidrug‑resistant osteosarcoma sublines and the molecular mechanisms of resistance

  • Authors:
    • Jian‑Zeng Yang
    • Shu‑Rong Ma
    • Xiao‑Li Rong
    • Mei‑Ju Zhu
    • Qiu‑Ye Ji
    • Ling‑Jie Meng
    • Yi‑Yao Gao
    • Yu‑Dan Yang
    • Yan Wang
  • View Affiliations / Copyright

    Affiliations: Scientific Research Center, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Endoscopy Center, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Gastroenterology and Hypothyroid Surgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
  • Pages: 3269-3276
    |
    Published online on: August 4, 2016
       https://doi.org/10.3892/mmr.2016.5590
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Yang JZ, Ma SR, Rong XL, Zhu MJ, Ji QY, Meng LJ, Gao YY, Yang YD and Wang Y: Characterization of multidrug‑resistant osteosarcoma sublines and the molecular mechanisms of resistance. Mol Med Rep 14: 3269-3276, 2016.
APA
Yang, J., Ma, S., Rong, X., Zhu, M., Ji, Q., Meng, L. ... Wang, Y. (2016). Characterization of multidrug‑resistant osteosarcoma sublines and the molecular mechanisms of resistance. Molecular Medicine Reports, 14, 3269-3276. https://doi.org/10.3892/mmr.2016.5590
MLA
Yang, J., Ma, S., Rong, X., Zhu, M., Ji, Q., Meng, L., Gao, Y., Yang, Y., Wang, Y."Characterization of multidrug‑resistant osteosarcoma sublines and the molecular mechanisms of resistance". Molecular Medicine Reports 14.4 (2016): 3269-3276.
Chicago
Yang, J., Ma, S., Rong, X., Zhu, M., Ji, Q., Meng, L., Gao, Y., Yang, Y., Wang, Y."Characterization of multidrug‑resistant osteosarcoma sublines and the molecular mechanisms of resistance". Molecular Medicine Reports 14, no. 4 (2016): 3269-3276. https://doi.org/10.3892/mmr.2016.5590
Copy and paste a formatted citation
x
Spandidos Publications style
Yang JZ, Ma SR, Rong XL, Zhu MJ, Ji QY, Meng LJ, Gao YY, Yang YD and Wang Y: Characterization of multidrug‑resistant osteosarcoma sublines and the molecular mechanisms of resistance. Mol Med Rep 14: 3269-3276, 2016.
APA
Yang, J., Ma, S., Rong, X., Zhu, M., Ji, Q., Meng, L. ... Wang, Y. (2016). Characterization of multidrug‑resistant osteosarcoma sublines and the molecular mechanisms of resistance. Molecular Medicine Reports, 14, 3269-3276. https://doi.org/10.3892/mmr.2016.5590
MLA
Yang, J., Ma, S., Rong, X., Zhu, M., Ji, Q., Meng, L., Gao, Y., Yang, Y., Wang, Y."Characterization of multidrug‑resistant osteosarcoma sublines and the molecular mechanisms of resistance". Molecular Medicine Reports 14.4 (2016): 3269-3276.
Chicago
Yang, J., Ma, S., Rong, X., Zhu, M., Ji, Q., Meng, L., Gao, Y., Yang, Y., Wang, Y."Characterization of multidrug‑resistant osteosarcoma sublines and the molecular mechanisms of resistance". Molecular Medicine Reports 14, no. 4 (2016): 3269-3276. https://doi.org/10.3892/mmr.2016.5590
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