Dados do Resumo

Título

ROLE OF GALECTIN-3 IN CASTRATION-RESISTANT PROSTATE CANCER

Introdução

Prostate cancer is the second leading cause of cancer-related deaths in men in Brazil. It often advances to an androgen-independent state, with few treatment options available and high mortality rates. Galectin-3, a glycoprotein, is highly expressed in both benign prostatic hyperplasia and prostate cancer, with elevated RNA levels in cancerous tissue compared to normal. Previous results from our laboratory demonstrated that, in castration-resistant prostate cancer cells (DU-145), estrogen receptor activation increases Galectin-3 expression, which is crucial for cell migration after estrogen treatment. However, the role of galectin-3 in prostate cancer remains to be elucidated.

Objetivo

This project aims to evaluate Galectin-3 in castration-resistant prostate cancer cell DU-145 and its interaction with cadherins, integrins, and estrogen receptors. The study includes Galectin-3 knockdown in DU-145 cells, analyses of gene expression, cellular proliferation, adhesion, and signaling pathways.

Métodos

DU-145 cells (androgen-resistant prostate cancer) were cultured in RPMI 1640 with 10% fetal bovine serum, HEPES, and gentamicin at 37°C with 5% CO2 for 72 hours, then switched to serum-free medium for 24 hours. Galectin-3 gene was silenced by transfection with lentivirus containing shRNA Gal-3, followed by selection with puromycin. Galectin-3 knockdown was confirmed by Western Blot and immunofluorescence assays. Galectin-3 knockdown cells were exposed to 17β-estradiol (10 nM) treatment for 24 hours. Cells were then counted in Neubaur chambers for proliferation assay.

Resultados

Western blot assay was performed using DU-145 wild-type (WT), scramble, and shGAL-3 cells, confirming the effectiveness of Galectin-3 knockdown. Cell Proliferation Assay was performed using DU-145 cells after treatment with 17β-Estradiol. DU-145 wild type (WT), scramble, or Galectin-3-silenced (shGAL-3) cells were treated with or without 17β-Estradiol (E2, 10 nM) for 24 hours. After treatment with 17β-Estradiol, an increase in the number of DU-145 WT (twofold) and scramble cells (almost threefold) compared to control cells (without 17β-estradiol) was observed. No increase was observed in DU-145 shGAL-3 cells treated with 17β-estradiol.

Conclusões

According to the cell proliferation assay results, 17β-estradiol promotes the proliferation of DU-145 WT and scramble cells, but the downregulation of Galectin-3 in shGAL-3 cells inhibits this process. Previous studies have shown that the activation of estrogen receptors increases the expression and signaling of Galectin-3 and promotes migration and invasion of DU-145 cells. Further studies are being performed to evaluate the role of Galectin-3 in adhesion and signaling pathways in DU-145 cancer cells. Therefore, our results indicate an interaction of Galectin-3 and estrogen receptor, promoting the tumorigenesis of prostate cancer cells.

Financiador do resumo

CAPES, FAPESP 2023/13622-1

Palavras Chave

Prostate cancer; Galectin-3; Estrogen receptors