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Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Mechanistic Study of Inhibitory Effects of Atorvastatin and Docetaxel in Combination on Prostate Cancer
Xuan Chen1, Yue Liu2, Jian Wu3
1Laboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. China Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, U.S.A.
Aim:
To investigate the effects and mechanisms of docetaxel and atorvastatin administered individually or in combination on prostate cancer cells.
Materials And Methods:
Cell growth and apoptosis were determined by the trypan blue exclusion assay and morphological assessment of cells was performed with propidium iodide. NF-κB activity was determined by luciferase reporter gene assay and the western blot assay was used to determine the levels of Bcl-2, phospho-Akt, VEGF, and phospho-Erk1/2.
Results:
Results showed that following pre-treatment with cholesterol, resistance of PC-3 prostate cancer cells to docetaxel was increased. The combination of docetaxel with atorvastatin potently inhibited growth and induced apoptosis in PC-3 cells. Mechanistic studies indicated that induction of apoptosis in PC-3 cells was associated with significant decreases in the levels of Bcl-2, VEGF, phosphor-Akt, and phosphor-Erk1/2.
Conclusion:
Treatment with cholesterol decreased the sensitivity of prostate cancer cells to docetaxel. Docetaxel in combination with cholesterol-lowering drugs such as atorvastatin may be an effective strategy for inhibiting the growth of prostate cancer.
Insights
Cholesterol increases prostate cancer cell resistance to docetaxel. Combining docetaxel with atorvastatin effectively inhibits cancer cell growth and induces apoptosis, offering a potential treatment strategy.
Area of Science:
- Oncology
- Pharmacology
Background:
- Cholesterol metabolism influences cancer cell behavior.
- Docetaxel is a standard chemotherapy for prostate cancer.
- Atorvastatin is a cholesterol-lowering drug with potential anticancer effects.
Purpose of the Study:
- To investigate the effects of docetaxel and atorvastatin on prostate cancer cells.
- To elucidate the mechanisms underlying their combined action.
- To assess the impact of cholesterol on docetaxel sensitivity.
Main Methods:
- Prostate cancer cell line (PC-3) was used.
- Cell viability and apoptosis were assessed.
- Western blot and luciferase assays were employed to analyze molecular pathways.
Main Results:
- Cholesterol pre-treatment enhanced docetaxel resistance in PC-3 cells.
- Combination therapy potently inhibited cell growth and induced apoptosis.
- Mechanisms involved decreased Bcl-2, VEGF, phospho-Akt, and phospho-Erk1/2 levels.
Conclusions:
- Cholesterol reduces prostate cancer cell sensitivity to docetaxel.
- Docetaxel combined with atorvastatin shows promise for prostate cancer treatment.
- Targeting cholesterol may enhance chemotherapy efficacy.
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