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Establishment and characterization of a cisplatin-resistant human neuroblastoma cell line
T Yasuno1, T Matsumura, T Shikata
1Department of Pediatrics, Kyoto Prefectural University of Medicine, Japan.
Background:
To investigate the mechanisms of cisplatin (CDDP)-resistance in neuroblastoma(NB), we established a CDDP-resistant human NB cell line, BM1R2.
Materials And Methods:
We characterized BM1R2 in terms of the susceptibilities to other anticancer agents, MDR1 and MRP expression, MYCN amplification, intracellular gultathione-S-transferase(GST-pi), metallothionein(MT) and gultathione(GSH) levels, and immunocytochemical and cytogenetic features.
Results:
When compared to parent BM1 line, BM1R2 exhibited a 17.0-fold resistance to CDDP and cross-resistance to other agents. MRP expression was only observed in BM1R2, whereas MDR1 was expressed in both lines. Notably higher intracellular GST-pi and MT levels were observed in BM1R2 cells. MYCN amplifications were 50 and 6 copies in BM1 and BM1R2, respectively, and additional aberrations were observed in chromosome 1 and 2 in BM1R2.
Conclusion:
It was suggested that GST-pi and MT could exert crucial roles on CDDP-resistance in our system. BM1R2 is of great interest for investigating the mechanisms of CDDP-resistance in NB.
Insights
This study developed a cisplatin-resistant neuroblastoma cell line (BM1R2) and found that elevated glutathione-S-transferase-pi (GST-pi) and metallothionein (MT) levels are key to cisplatin resistance in neuroblastoma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Neuroblastoma (NB) is a pediatric cancer with challenges in treatment resistance.
- Cisplatin (CDDP) is a common chemotherapy agent used for NB.
- Understanding CDDP resistance mechanisms is crucial for improving NB treatment outcomes.
Purpose of the Study:
- To establish and characterize a cisplatin-resistant human neuroblastoma cell line (BM1R2).
- To investigate the molecular mechanisms underlying CDDP resistance in neuroblastoma.
- To identify potential biomarkers for CDDP resistance in NB.
Main Methods:
- Established a CDDP-resistant NB cell line (BM1R2) from a parent line (BM1).
- Assessed cross-resistance to other anticancer agents.
- Quantified multidrug resistance protein (MRP) and multidrug resistance 1 (MDR1) expression.
- Measured intracellular glutathione-S-transferase (GST-pi), metallothionein (MT), and glutathione (GSH) levels.
- Analyzed MYCN amplification and performed cytogenetic analysis.
Main Results:
- BM1R2 showed a 17.0-fold resistance to CDDP with cross-resistance to other agents.
- MRP expression was specific to BM1R2, while MDR1 was present in both cell lines.
- BM1R2 cells exhibited significantly higher intracellular GST-pi and MT levels.
- MYCN amplification decreased in BM1R2, with chromosomal aberrations noted in chromosomes 1 and 2.
Conclusions:
- GST-pi and MT are suggested to play critical roles in CDDP resistance in this neuroblastoma model.
- The BM1R2 cell line serves as a valuable tool for further research into CDDP resistance mechanisms in NB.
- Findings may inform the development of strategies to overcome chemotherapy resistance in neuroblastoma.