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Tumor necrosis factor-alpha related gene response to Epothilone B in ovarian cancer
Dineo Khabele1, Melissa Lopez-Jones, WanCai Yang
1Albert Einstein Cancer Center and Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA. dkhabele@montefiore.org
Objectives:
Epothilone B (EpoB) is a non-taxane microtubule-stabilizing agent with a mode of action similar to that of paclitaxel, but with the advantage of being active in paclitaxel-resistant cells. Knowledge regarding other mechanisms of EpoB action is limited. The purpose of this study was to identify gene expression profiles associated with the biological response to EpoB in an ovarian cancer cell line (SKOV3).
Methods:
SKOV3 cells were maintained in McCoy's 5A media. Equal densities cells were treated with or without EpoB, and were evaluated for cell growth arrest and apoptosis. mRNA expression was evaluated by cDNA microarrays and quantitative, real time reverse transcription polymerase chain reaction (QRTPCR).
Results:
EpoB (10 nM) led to cell cycle arrest and apoptosis in SKOV3 cells. Microarray analysis, comparing EpoB-treated to untreated cells, revealed altered expression of 41 genes. There was a predominance of sequences related to the TNFalpha stress response pathway. Differential expression of selected genes was confirmed by QRTPCR.
Conclusions:
We demonstrated that cDNA microarrays are a useful tool to rapidly screen for patterns of gene expression that characterize drug response. The microarray data suggest that the microtubule-stabilizing agent, EpoB, triggers stress-related signal transduction pathways related to TNFalpha. These pathways may contribute to mechanisms of EpoB action and potential mechanisms of resistance in ovarian cancer.
Insights
Epothilone B (EpoB) triggers stress pathways in ovarian cancer cells, offering insights into its action and resistance mechanisms. This microtubule-stabilizing agent shows promise beyond paclitaxel resistance.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Epothilone B (EpoB) is a microtubule-stabilizing agent effective in paclitaxel-resistant cancers.
- Limited knowledge exists regarding EpoB's broader mechanisms of action.
Purpose of the Study:
- To identify gene expression profiles linked to the biological response of EpoB in SKOV3 ovarian cancer cells.
- To explore novel pathways affected by EpoB treatment.
Main Methods:
- SKOV3 ovarian cancer cells were treated with Epothilone B.
- Cell cycle arrest and apoptosis were assessed.
- Gene expression changes were analyzed using cDNA microarrays and quantitative real-time PCR (QRTPCR).
Main Results:
- Epothilone B induced cell cycle arrest and apoptosis in SKOV3 cells.
- Microarray analysis revealed altered expression of 41 genes.
- A significant number of altered genes were associated with the TNFalpha stress response pathway.
- QRTPCR confirmed differential expression of selected genes.
Conclusions:
- cDNA microarrays are effective for rapid screening of drug response gene expression patterns.
- Epothilone B activates TNFalpha-related stress signaling pathways.
- These pathways may elucidate Epothilone B's action and resistance mechanisms in ovarian cancer.
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