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Updated: Aug 10, 2026
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Screening of an annotated compound library for drug activity in a resistant myeloma cell line
Linda Rickardson1, Mårten Fryknäs, Caroline Haglund
1Department of Medical Sciences, Division of Clinical Pharmacology, Uppsala University, 751 85, Uppsala, Sweden. Linda.Rickardson@medsci.uu.se
Purpose:
Resistance to anticancer drugs is a major problem in chemotherapy. In order to identify drugs with selective cytotoxic activity in drug-resistant cancer cells, the annotated compound library LOPAC1280, containing compounds from 56 pharmacological classes, was screened in the myeloma cell line RPMI 8226 and its doxorubicin-resistant subline 8226/Dox40.
Methods:
Cell survival was measured by the Fluorometric Microculture Cytotoxicity Assay.
Results:
Selective cytotoxic activity in 8226/Dox40 was obtained for 33 compounds, with the most pronounced difference observed for the glucocorticoids. A microarray analysis of the cells showed a difference in mRNA-expression for the glucocorticoid receptor suggesting potential mechanisms for the difference in glucocorticoid sensitivity. In the presence of the glucocorticoid-receptor antagonist RU486, the sensitivity to the glucocorticoids was reduced and a similar effect level in RPMI 8226 and 8226/Dox40 was achieved.
Conclusion:
In conclusion, screening of mechanistically annotated compounds on drug-resistant cancer cells can identify compounds with selective activity and provide a basis for the development of novel treatments of drug-resistant malignancies.
Insights
This study screened drug libraries against resistant myeloma cells, identifying glucocorticoids as selectively cytotoxic. This finding offers a basis for developing new treatments for drug-resistant cancers.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Anticancer drug resistance poses a significant challenge in chemotherapy.
- Identifying novel therapeutic agents effective against resistant cancer cells is crucial.
Purpose of the Study:
- To screen a library of mechanistically annotated compounds for selective cytotoxic activity in drug-resistant myeloma cells.
- To identify potential drug candidates for overcoming chemotherapy resistance.
Main Methods:
- Utilized the RPMI 8226 myeloma cell line and its doxorubicin-resistant subline, 8226/Dox40.
- Employed the Fluorometric Microculture Cytotoxicity Assay to measure cell survival.
- Conducted microarray analysis to investigate gene expression differences.
Main Results:
- Identified 33 compounds with selective cytotoxic activity against the resistant 8226/Dox40 cell line.
- Glucocorticoids exhibited the most pronounced selective activity.
- Differential mRNA expression of the glucocorticoid receptor was observed, suggesting a role in sensitivity.
Conclusions:
- Screening annotated compounds against resistant cancer cells can identify selective agents.
- This approach provides a foundation for developing new therapies for drug-resistant malignancies.
- Glucocorticoids show promise as selective agents against doxorubicin-resistant myeloma.
