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Screening of an ann...
Screening of an annotated compound library for drug activity in a resistant myeloma cell line
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- Rickardson, Linda (author)
- Uppsala universitet,Klinisk farmakologi,Cancer Pharmacology and Informatics
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- Fryknäs, Mårten (author)
- Uppsala universitet,Institutionen för genetik och patologi,Cancer Pharmacology and Informatics
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- Haglund, Caroline (author)
- Uppsala universitet,Klinisk farmakologi,Cancer Pharmacology and Informatics
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- Lövborg, Henrik (author)
- Uppsala universitet,Klinisk farmakologi,Cancer Pharmacology and Informatics
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- Nygren, Peter (author)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,Cancer Pharmacology and Informatics
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- Gustafsson, Mats (author)
- Uppsala universitet,Institutionen för genetik och patologi,Signalbehandling,Cancer Pharmacology and Informatics
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- Isaksson, Anders (author)
- Uppsala universitet,Institutionen för genetik och patologi,Cancer Pharmacology and Informatics
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- Larsson, Rolf (author)
- Uppsala universitet,Klinisk farmakologi,Cancer Pharmacology and Informatics
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(creator_code:org_t)
- 2006-03-10
- 2006
- English.
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In: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 58:6, s. 749-758
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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 LOPAC(1280), 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.
Keyword
- anticancer drug resistance
- drug screening
- annotated compound library
- glucocorticoids
- gene expression
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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