Abstract | PURPOSE: METHODS: Human ovarian carcinoma cells (1A9 cells) and murine T cells were treated with different combinations of microtubule-stabilizing or destabilizing agents. The compounds were given individually and in combination, and the antiproliferative activity was assessed to calculate a combination index (CI) from the equation: CI = D(1)/Dx(1) + D(2)/Dx(2) in which D(1) and D(2) are the concentrations of drug 1 and drug 2 that when given together give the same response as drug 1 and 2 alone (Dx(1) and Dx(2)). Thus, a CI value of less than 1.0 indicates a synergistic effect between the two drugs in which the response to the two drugs given together is greater than the additive response of the two drugs if given on their own. RESULTS: CONCLUSIONS: Combining two microtubule-targeting agents with different binding sites does not guarantee a synergistic interaction in cells, and additional factors are likely to be involved. This study highlights the importance of preclinical testing of actual combinations of drugs before proceeding into clinical trials.
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Authors | Anja Wilmes, David O'Sullivan, Ariane Chan, Clarissa Chandrahasen, Ian Paterson, Peter T Northcote, Anne Camille La Flamme, John H Miller |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 68
Issue 1
Pg. 117-26
(Jul 2011)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 20848285
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bridged Bicyclo Compounds, Heterocyclic
- Lactones
- Macrolides
- Tubulin Modulators
- laulimalide
- peloruside A
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Topics |
- Animals
- Bridged Bicyclo Compounds, Heterocyclic
(chemistry, pharmacology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cells, Cultured
- Drug Synergism
- Female
- Humans
- Inhibitory Concentration 50
- Lactones
(chemistry, pharmacology)
- Macrolides
(chemistry, pharmacology)
- Mice
- Mice, Inbred C57BL
- Microtubules
(drug effects)
- Ovarian Neoplasms
(drug therapy, pathology)
- Spleen
- T-Lymphocytes
(drug effects)
- Tubulin Modulators
(pharmacology)
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