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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Enhancing prostate cancer cells' sensitivity to flutamide by resveratrol: An in-vitro study
Seyedeh Fatemeh Hosseini1, Seyed Reza Yahyazadeh2, Akram Mirzaei1
1Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Background:
As the most common cancer in men, and its progression poses a significant challenge. New and effective treatment strategies are needed to improve outcomes for patients with prostate cancer. This study examined if resveratrol, a natural substance, could improve prostate cancer cell lines' response to flutamide, a standard antiandrogenic treatment for untreated prostate cancer, while minimizing adverse effects.
Method:
MTT assay was used to quantify resveratrol and flutamide IC50 values, Annexin-V/PI staining for apoptosis, PI staining for DNA cell cycle, and real-time PCR for BAX, BCL-2, VEGFC, HIF-1α, Snail1, E-Cadherin, and KLK3 mRNA levels Scratch-wound, colony-forming, and Hoechst staining analyzed cell migration, proliferation, and nucleus morphology. Spheroid creation in 3D was also considered. All tests used LNCaP, DU145, and PC3 prostate cancer cell lines at various stages.
Results:
Resveratrol, when combined with flutamide, can reduce malignant cell migration, colony formation, and proliferation and promote apoptosis in prostate cancer cell lines. Even in androgen-unresponsive cell lines (DU145 and PC3), it may benefit flutamide prostate cancer treatment. Apoptosis genes (BAX) were upregulated in LNCaP, DU145, and PC3 cancer cell lines when administered alone or with flutamide. Additionally, flutamide might significantly lower BCL-2 levels in PC3 cells. When combined with flutamide, resveratrol increased apoptosis and altered the expression of genes involved in angiogenesis (VEGFC), epithelial-mesenchymal transition (EMT, Snail1 and E-Cadherin), and prostate cancer biomarker (KLK3) in prostate cancer cell lines.
Conclusion:
Resveratrol reduced the dose of flutamide in the treatment of prostate cancer cell lines (LNCaP, DU145, and PC3) and improved its side effects, as well as increasing the sensitivity of cells to flutamide treatment.
Insights
Resveratrol enhances flutamide treatment for prostate cancer by reducing required dosage and improving efficacy. This natural compound promotes apoptosis and inhibits cancer cell growth, offering a promising strategy for managing prostate cancer.
Area of Science:
- Oncology
- Pharmacology
- Natural Products Research
Background:
- Prostate cancer is the most common cancer in men, necessitating novel treatment strategies.
- Current treatments face challenges in efficacy and side effects.
- Investigating natural compounds like resveratrol offers potential therapeutic benefits.
Purpose of the Study:
- To evaluate resveratrol's potential to enhance flutamide efficacy in prostate cancer.
- To assess the impact of resveratrol on prostate cancer cell response to flutamide.
- To determine if resveratrol can minimize adverse effects associated with flutamide treatment.
Main Methods:
- Utilized MTT assays to determine IC50 values for resveratrol and flutamide.
- Employed Annexin-V/PI and Hoechst staining for apoptosis and nucleus morphology analysis.
- Conducted real-time PCR to analyze gene expression related to apoptosis, EMT, and angiogenesis.
Main Results:
- Combined resveratrol and flutamide reduced prostate cancer cell migration, proliferation, and colony formation.
- Resveratrol upregulated apoptosis-related genes (BAX) and influenced BCL-2 levels.
- The combination therapy altered expression of genes involved in angiogenesis (VEGFC) and epithelial-mesenchymal transition (EMT).
Conclusions:
- Resveratrol reduced the effective dose of flutamide for prostate cancer cell lines.
- Resveratrol improved flutamide's side effect profile and increased cellular sensitivity.
- This combination therapy presents a promising approach for prostate cancer treatment.

