Adiponectin receptor agonist, AdipoRon, reduces the growth of prostate cancer cells and patient-derived organoids

IF 6.4 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2026-02-15 Epub Date: 2025-12-26 DOI:10.1016/j.lfs.2025.124175

Francielle C. Mosele , Ana Luiza Romano Gabriel , Nilton José dos Santos , Caroline Nascimento Barquilha , Caio Cesar Damasceno Monção , Micheli Canuto de Lima , Mark A. Rubin , Sérgio Luis Felisbino , Joanna Triscott

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引用次数: 0

Abstract

Low adiponectin levels in obese men are associated with an incidence of aggressive prostate cancer (PCa). Despite significant advances in PCa treatment, some cases become resistant, making the development of new therapies crucial. An alternative treatment is the use of agonists, such as AdipoRon. Here, we elucidate the antitumor effects of AdipoRon on PCa models and demonstrate reduced cell proliferation, migration, and invasion in vitro. AdipoRon impaired mitochondrial respiration of androgen-dependent and castration-resistant cells. We show that this agonist reduces AR and PSA expression in androgen-dependent prostate cells. Adiponectin receptors (AdipoR1 and AdipoR2) were upregulated in PC3 and DU-145 cells. We hypothesize that the alteration of PPAR alpha could explain the effects of AdipoRon. Additionally, the antigrowth effects of AdipoRon were observed in the patient-derived organoids PM154 and MSK-PCa16. Our findings reveal that AdipoRon has strong in vitro antitumor effects on PCa, supporting its potential as a promising therapeutic candidate. Future studies should focus on in vivo models to validate these effects and explore the underlying mechanisms, which may open new therapies for PCa.

Statement of implication

AdipoRon decreases prostate cancer cell growth.

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脂联素受体激动剂，AdipoRon，减少前列腺癌细胞和患者来源的类器官的生长。

肥胖男性低脂联素水平与侵袭性前列腺癌（PCa）的发病率相关。尽管前列腺癌治疗取得了重大进展，但一些病例变得耐药，这使得开发新的治疗方法至关重要。另一种治疗方法是使用激动剂，如AdipoRon。在这里，我们阐明了AdipoRon对PCa模型的抗肿瘤作用，并在体外证明了细胞增殖、迁移和侵袭的减少。AdipoRon损害雄激素依赖细胞和去势抵抗细胞的线粒体呼吸。我们发现这种激动剂可以降低雄激素依赖性前列腺细胞中AR和PSA的表达。脂联素受体AdipoR1和AdipoR2在PC3和DU-145细胞中表达上调。我们假设PPAR α的改变可以解释AdipoRon的作用。此外，在患者来源的类器官PM154和MSK-PCa16中观察到AdipoRon的抗生长作用。我们的研究结果表明，AdipoRon对PCa具有很强的体外抗肿瘤作用，支持其作为有希望的治疗候选药物的潜力。未来的研究应该集中在体内模型上，以验证这些效应并探索潜在的机制，这可能会为PCa开辟新的治疗方法。结论：脂肪素可降低前列腺癌细胞的生长。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.