Prostate cancer (PCa) progression is associated with epithelial-to-mesenchymal transition (EMT), characterized by loss of epithelial and gain of mesenchymal markers, which promotes tumor invasion and therapy resistance. PCa patients show reduced serum adiponectin (APN) levels, which are associated with aggressive disease. APN receptors, AdipoR1/R2, can be activated by agonists such as AdipoRon (ADR). Previous studies have shown that ADR has potent antitumor effects in several types of cancer; however, its effect on PCa has not been explored. Therefore, this study aimed to investigate the effect of AR in PCa cells grown in 3D spheroids. DU145 and PC3 cells (5 × 10⁴) were seeded in an agarose-coated plate, treated with 0 (CT) or 150µM ADR for 48h. Gene expression of AdipoR1/R2 and EMT markers was analyzed by RT-qPCR, and MMP-2/-9 activity by zymography. E-cadherin expression was low in PC3 compared to DU145 (p<0.05) and increased by 110% in DU145 cells after ADR treatment. N-cadherin showed higher expression in PC3 than DU145 in CT (p<0.05) and ADR (p<0.01) treatments. Vimentin levels were unaffected by ADR. Snail was lower in PC3 than DU145 after ADR treatment (p<0.05). Twist was upregulated in PC3 cells compared to DU145 (p<0.01) and decreased by 57,56% in PC3 after ADR treatment. Zeb1 was similarly expressed in both conditions. In PC3, APN receptors were not modulated after ADR. DU145 cells showed increased expression of AdipoR1 (378%) and AdipoR2 (316%) after ADR compared with CT. MMP-9 was upregulated by ADR in PC3 (6,3% vs CT) and DU145 (22,4% vs CT). MMP-2/TIMP2 ratio was decreased by 36% in ADR-treated compared to CT in DU145 and 41% in PC3, and MMP-9/TIMP-1 decreased 73% in DU145 ADR. These results confirm the epithelial-like DU145 and mesenchymal-like PC3 phenotypes, show ADR-mediated modulation of gene expression for EMT markers, and suggest ADR may reduce the invasive potential of PCa cells. Protein level analyses are necessary to confirm these findings.
AdipoRon Modulates EMT Markers and invasive potential in Prostate Cancer Spheroids / A. Luiza Romano Gabriel, S. Vinci, M. Anselmi, M. Sommariva, S. Luis Felisbino, N. Gagliano. 39. Reunião Anual da Federação de Sociedades de Biologia Experimental (FeSBE) Campinas/SP 2025.
AdipoRon Modulates EMT Markers and invasive potential in Prostate Cancer Spheroids
S. VinciCo-primo
;M. Anselmi;M. Sommariva;N. Gagliano
Ultimo
2025
Abstract
Prostate cancer (PCa) progression is associated with epithelial-to-mesenchymal transition (EMT), characterized by loss of epithelial and gain of mesenchymal markers, which promotes tumor invasion and therapy resistance. PCa patients show reduced serum adiponectin (APN) levels, which are associated with aggressive disease. APN receptors, AdipoR1/R2, can be activated by agonists such as AdipoRon (ADR). Previous studies have shown that ADR has potent antitumor effects in several types of cancer; however, its effect on PCa has not been explored. Therefore, this study aimed to investigate the effect of AR in PCa cells grown in 3D spheroids. DU145 and PC3 cells (5 × 10⁴) were seeded in an agarose-coated plate, treated with 0 (CT) or 150µM ADR for 48h. Gene expression of AdipoR1/R2 and EMT markers was analyzed by RT-qPCR, and MMP-2/-9 activity by zymography. E-cadherin expression was low in PC3 compared to DU145 (p<0.05) and increased by 110% in DU145 cells after ADR treatment. N-cadherin showed higher expression in PC3 than DU145 in CT (p<0.05) and ADR (p<0.01) treatments. Vimentin levels were unaffected by ADR. Snail was lower in PC3 than DU145 after ADR treatment (p<0.05). Twist was upregulated in PC3 cells compared to DU145 (p<0.01) and decreased by 57,56% in PC3 after ADR treatment. Zeb1 was similarly expressed in both conditions. In PC3, APN receptors were not modulated after ADR. DU145 cells showed increased expression of AdipoR1 (378%) and AdipoR2 (316%) after ADR compared with CT. MMP-9 was upregulated by ADR in PC3 (6,3% vs CT) and DU145 (22,4% vs CT). MMP-2/TIMP2 ratio was decreased by 36% in ADR-treated compared to CT in DU145 and 41% in PC3, and MMP-9/TIMP-1 decreased 73% in DU145 ADR. These results confirm the epithelial-like DU145 and mesenchymal-like PC3 phenotypes, show ADR-mediated modulation of gene expression for EMT markers, and suggest ADR may reduce the invasive potential of PCa cells. Protein level analyses are necessary to confirm these findings.
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