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Updated: Mar 16, 2026
Author Spotlight: Replicating Human Osteosarcoma Progression in Immunodeficient Mice for Cancer Study
Published on: March 22, 2024
Characterization of multidrug‑resistant osteosarcoma sublines and the molecular mechanisms of resistance
Jian-Zeng Yang1, Shu-Rong Ma2, Xiao-Li Rong1
1Scientific Research Center, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
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.
Insights
Multidrug resistance (MDR) in osteosarcoma is complex. This study developed resistant cell lines, revealing that molecular changes and cell morphology vary with resistance levels, suggesting heterogeneity drives MDR.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Multidrug resistance (MDR) poses a significant challenge in cancer treatment, with underlying molecular mechanisms often remaining unclear.
- Osteosarcoma treatment is hindered by the development of resistance to chemotherapeutic agents.
Purpose of the Study:
- To establish and characterize vincristine-resistant MG63 osteosarcoma cell sublines.
- To investigate the molecular mechanisms and phenotypic changes associated with increasing levels of drug resistance.
Main Methods:
- Development of four MG63/VCR cell sublines with increasing resistance to vincristine (VCR).
- Assessment of drug resistance indices (RI) using CCK-8 assays.
- Evaluation of cross-resistance, proliferation, migration, and expression of key genes (MDR1, topoisomerase II, LIM kinase 1, GST-π) via various molecular techniques.
Main Results:
- Established MG63/VCR sublines with RI ranging from 163 to 2,707-fold higher than parental cells, exhibiting cross-resistance to other chemotherapeutics.
- Observed reduced proliferation and altered cell morphology (pseudopodia, cytoplasmic processes) with increasing RI.
- Found variable expression patterns of drug resistance-associated genes; MDR1 increased, while MDR-associated protein 1, topoisomerase II, and LIM kinase 1 decreased in highly resistant cells.
Conclusions:
- Molecular alterations associated with drug resistance are not uniform and can change with the degree of resistance.
- Intratumoral clonal and phenotypic heterogeneity may play a crucial role in the development of MDR in osteosarcoma.
- The developed MG63/VCR sublines serve as a valuable model for studying MDR mechanisms and identifying strategies to overcome resistance in human osteosarcoma.
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