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Updated: Aug 9, 2026
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Use of human neuroblastoma continuous cell lines for in vitro drug sensitivity screening
B T Hill1, R D Whelan, L K Hosking
1Laboratory of Cellular Chemotherapy, Imperial Cancer Research Fund, London, United Kingdom.
Abstract:
We have used three continuous human neuroblastoma cell lines to establish patterns of in vitro drug sensitivities, as judged by clonogenic assay. We evaluated 12 'standard' antitumor drugs already in clinical usage, and tested four newer analogues, one of cisplatin and three of doxorubicin, and the investigational agent desferrioxamine. A certain heterogeneity of drug sensitivities was noted amongst these three cell lines, but a few general conclusions can be drawn. Responses of all lines tested were similar for actinomycin D, dibromodulcitol, doxorubicin, 5-fluorouracil, melphalan and VM 26. However, line CHP 100 proved hypersensitive to amsacrine, bleomycin, methotrexate and vincristine yet refractory to cisplatin, carboplatin and VP-16, compared with the other two lines. This emphasizes the necessity for using a panel of cell lines for this type of drug screening programme. A comparison of IC50 drug concentrations, derived from these in vitro tests, with plasma levels achievable clinically, indicate that VP-16, VM 26, doxorubicin and cisplatin appear to be the most effective agents in this tumor type. This finding is consistent with clinical experience. The newer doxorubicin analogues proved 2-5 fold more cytotoxic than doxorubicin itself. However, these differences also appear to be reflected in the lower dose ranges now being tested in phase I/II clinical trials. Desferrioxamine, which proved cytotoxic against all three neuroblastoma cell lines, exerted comparable cytotoxicity against two of the three non-neuroblastoma human tumor cell lines evaluated. Therefore we suggest that attempts to identify any specific antineuroblastoma activities by new investigational agents using this type of model systems require evaluation against panels of both neuroblastoma and non-neuroblastoma lines.
Insights
This study screened neuroblastoma cell lines against various chemotherapy drugs, finding VP-16, VM 26, doxorubicin, and cisplatin most effective. Newer doxorubicin analogues showed increased cytotoxicity, and desferrioxamine was also effective.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Neuroblastoma is a significant pediatric cancer.
- Understanding in vitro drug sensitivity is crucial for developing effective treatments.
- Standard and novel chemotherapeutic agents require rigorous preclinical evaluation.
Purpose of the Study:
- To establish in vitro drug sensitivity patterns for human neuroblastoma cell lines.
- To compare the efficacy of standard antitumor drugs, doxorubicin analogues, and desferrioxamine.
- To assess the necessity of using multiple cell lines for comprehensive drug screening.
Main Methods:
- Utilized three continuous human neuroblastoma cell lines.
- Performed clonogenic assays to evaluate drug sensitivities.
- Tested 12 standard antitumor drugs, 4 newer analogues (cisplatin, doxorubicin), and desferrioxamine.
Main Results:
- Observed heterogeneity in drug sensitivities among cell lines.
- Identified actinomycin D, dibromodulcitol, doxorubicin, 5-fluorouracil, melphalan, and VM 26 as having similar responses across lines.
- CHP 100 cell line showed hypersensitivity to amsacrine, bleomycin, methotrexate, vincristine, and refractoriness to cisplatin, carboplatin, VP-16.
- VP-16, VM 26, doxorubicin, and cisplatin were identified as most effective agents based on IC50 values and achievable plasma levels.
- Newer doxorubicin analogues demonstrated 2-5 fold greater cytotoxicity than doxorubicin.
- Desferrioxamine exhibited cytotoxicity against all tested neuroblastoma and some non-neuroblastoma cell lines.
Conclusions:
- A panel of cell lines is essential for accurate drug screening in neuroblastoma.
- VP-16, VM 26, doxorubicin, and cisplatin show promise for neuroblastoma treatment.
- Novel doxorubicin analogues warrant further clinical investigation.
- Evaluation of investigational agents requires testing against both neuroblastoma and non-neuroblastoma cell lines to determine specific activity.
