Naiki-Ito Aya, Naiki Taku, Takahashi Satoru
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Pathol Int. 2025 Mar;75(3):131-144. doi: 10.1111/pin.13509. Epub 2025 Jan 14.
Prostate cancer (PCa) is the second most common cancer in men globally. Its growth is driven by oxidative stress associated with inflammation, aging, and environmental factors, including diet and lifestyle. These factors contribute to multiple stages of PCa progression, including progression to castration-resistant prostate cancer (CRPC). Therefore, oxidative stress represents an intriguing target for PCa chemoprevention and treatment. In vivo experimental models are crucial for understanding the mechanisms of PCa development, validating chemopreventive and therapeutic approaches, and translating preclinical results into clinical applications. We established a transgenic rat for adenocarcinoma of the prostate (TRAP) model, a transgenic rat that efficiently develops androgen-dependent adenocarcinoma, pathologically and biologically mimicking human PCa progression, to clarify the mechanisms of tumor progression, including the involvement of oxidative stress, and established a system for screening the chemopreventive effects of agents against PCa. Additionally, we derived a CRPC model from the TRAP model and developed a distant metastasis model, providing a comprehensive multistage rat model of prostate carcinogenesis. This review presents findings on the molecular mechanisms of PCa and the chemopreventive effects of natural compounds with antioxidant properties, such as polyphenols. We additionally described the potential for repositioning existing drugs with antiandrogenic activity for PCa chemoprevention.
前列腺癌（PCa）是全球男性中第二常见的癌症。其生长由与炎症、衰老以及包括饮食和生活方式在内的环境因素相关的氧化应激驱动。这些因素促成了前列腺癌进展的多个阶段，包括进展为去势抵抗性前列腺癌（CRPC）。因此，氧化应激是前列腺癌化学预防和治疗中一个引人关注的靶点。体内实验模型对于理解前列腺癌发展机制、验证化学预防和治疗方法以及将临床前结果转化为临床应用至关重要。我们建立了前列腺腺癌转基因大鼠（TRAP）模型，这是一种能高效发展雄激素依赖性腺癌的转基因大鼠，在病理和生物学上模拟人类前列腺癌进展，以阐明肿瘤进展机制，包括氧化应激的参与情况，并建立了一个筛选药物对前列腺癌化学预防作用的系统。此外，我们从TRAP模型衍生出CRPC模型并建立了远处转移模型，提供了一个全面的前列腺癌发生多阶段大鼠模型。本综述介绍了前列腺癌分子机制以及具有抗氧化特性的天然化合物（如多酚）的化学预防作用的相关研究结果。我们还描述了重新利用具有抗雄激素活性的现有药物进行前列腺癌化学预防的潜力。
