Hosseini Seyedeh Fatemeh, Yahyazadeh Seyed Reza, Mirzaei Akram, Mashhadi Rahil, Ghajar Helia Azodian, Taheri Diana, Aghamir Seyed Mohammad Kazem
Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Department of Urology, Shariati Hospital, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Tissue Cell. 2025 Jun;94:102807. doi: 10.1016/j.tice.2025.102807. Epub 2025 Feb 21.
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.
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.
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.
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.
前列腺癌是男性最常见的癌症,其进展带来了重大挑战。需要新的有效治疗策略来改善前列腺癌患者的治疗效果。本研究探讨了天然物质白藜芦醇是否能改善前列腺癌细胞系对氟他胺(一种用于未经治疗的前列腺癌的标准抗雄激素治疗药物)的反应,同时将不良反应降至最低。
采用MTT法测定白藜芦醇和氟他胺的IC50值,用膜联蛋白V/碘化丙啶染色检测细胞凋亡,用碘化丙啶染色分析DNA细胞周期,用实时PCR检测BAX、BCL-2、VEGFC、HIF-1α、Snail1、E-钙黏蛋白和KLK3 mRNA水平。通过划痕实验、集落形成实验和Hoechst染色分析细胞迁移、增殖和细胞核形态。还考虑了三维球体的形成。所有实验均使用处于不同阶段的LNCaP、DU145和PC3前列腺癌细胞系。
白藜芦醇与氟他胺联合使用时,可减少前列腺癌细胞系中恶性细胞的迁移、集落形成和增殖,并促进细胞凋亡。即使在雄激素无反应的细胞系(DU145和PC3)中,它也可能有益于氟他胺治疗前列腺癌。单独使用或与氟他胺联合使用时,LNCaP、DU145和PC3癌细胞系中的凋亡基因(BAX)均上调另外,氟他胺可能会显著降低PC3细胞中的BCL-2水平。白藜芦醇与氟他胺联合使用时,可增加前列腺癌细胞系中的细胞凋亡,并改变与血管生成(VEGFC)、上皮-间质转化(EMT,Snail1和E-钙黏蛋白)以及前列腺癌生物标志物(KLK3)相关的基因表达。
白藜芦醇在治疗前列腺癌细胞系(LNCaP、DU145和PC3)时可降低氟他胺的剂量,改善其副作用,并增加细胞对氟他胺治疗的敏感性。