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Updated: May 22, 2026
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
The use of LC-MS to identify differentially expressed proteins in docetaxel-resistant prostate cancer cell lines
Kathleen O'Connell1, Maria Prencipe, Amanda O'Neill
1MTCI, National Institute for Cellular Biotechnology, DCU, Glasnevin, Dublin, Ireland. Kathleen.OConnell@dcu.ie
Abstract:
Docetaxel is a taxane-derived chemotherapy drug that has been approved for treatment of prostate cancer. While docetaxel is frequently used as a treatment for hormone-refractory prostate cancer, a subset of patients either do not respond to this treatment or those that do respond eventually become resistant to the drug over time. Resistance to docetaxel is complex and multi-factoral and further understanding of the cellular biochemistry underlying resistance is vital to improve treatment efficacy. To identify proteins altered in the resistant phenotype, three parental cell lines DU145, 22RV1 and PC-3, as well as their docetaxel resistant sub-lines, were subjected to quantitative label-free LC-MS proteomic profiling. A total of 189 significant (p < 0.05) protein abundance changes were identified in the DU145 resistant sub-lines, 254 in the 22RV1 sub-lines, and 51 and 72 in the 8 and 12 nM resistant PC-3 sub-lines, respectively. From these, 29 proteins demonstrated a significant (p < 0.05) fold change across two or more resistant variants. These included proteins indicative of an epithelial-to-mesenchemyl transition as well as altered heat shock response elements.
Insights
Understanding docetaxel resistance in prostate cancer is crucial. This study identified key protein changes, including those related to epithelial-to-mesenchymal transition, in resistant cancer cells, offering new therapeutic targets.
Area of Science:
- Oncology
- Proteomics
- Cellular Biochemistry
Background:
- Docetaxel is a primary chemotherapy for prostate cancer, but resistance develops in some patients.
- Mechanisms of docetaxel resistance are complex and not fully understood.
- Improved understanding of resistance biochemistry is vital for enhancing treatment efficacy.
Purpose of the Study:
- To identify protein alterations associated with docetaxel resistance in prostate cancer cell lines.
- To investigate the proteomic landscape of docetaxel-resistant phenotypes.
- To uncover potential biomarkers and therapeutic targets for overcoming resistance.
Main Methods:
- Quantitative label-free liquid chromatography-mass spectrometry (LC-MS) proteomic profiling was performed.
- Three prostate cancer cell lines (DU145, 22RV1, PC-3) and their docetaxel-resistant sub-lines were analyzed.
- Statistical analysis identified significant protein abundance changes (p < 0.05).
Main Results:
- Significant protein abundance changes were observed across resistant cell lines (189 in DU145, 254 in 22RV1, 51-72 in PC-3).
- Twenty-nine proteins showed significant fold changes across multiple resistant variants.
- Identified proteins were associated with epithelial-to-mesenchymal transition and altered heat shock responses.
Conclusions:
- Proteomic profiling reveals distinct molecular signatures in docetaxel-resistant prostate cancer cells.
- Alterations in epithelial-to-mesenchymal transition and heat shock proteins are implicated in resistance.
- These findings provide insights into resistance mechanisms and potential therapeutic strategies.
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