Chiu Melody, McBeth Lucien, Sindhwani Puneet, Hinds Terry D
Center for Hypertension and Personalized Medicine, Department of Physiology & Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
Department of Urology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
PPAR Res. 2017;2017:4810672. doi: 10.1155/2017/4810672. Epub 2017 Feb 28.
The use of thiazolidinedione (TZD) therapy in type II diabetic patients has proven useful in the lowering of blood glucose levels. However, recent investigations have shown that there may be potential health concerns associated, including the risk of developing bladder cancer as well as complications in the cardiovasculature. TZDs are ligands for the nuclear receptor PPAR, and activation causes lipid uptake and insulin sensitization, both of which are critical processes for diabetic patients whose bodies are unable to utilize insulin effectively. Several studies have shown that PPAR/TZDs decrease IGF-1 levels and, thus, reduce cancer growth in carcinomas such as the pancreas, colon, liver, and prostate. However, other studies have shed light on the potential of the receptor as a biomarker for uroepithelial carcinomas, particularly due to its stimulatory effect on migration of bladder cancer cells. Furthermore, PPAR may provide the tumor-promoting microenvironment by de novo synthesis of nutrients that are needed for bladder cancer development. In this review, we closely examine the TZD class of drugs and their effects on PPAR in patient studies along with additional molecular factors that are positive modulators, such as protein phosphatase 5 (PP5), which may have considerable implications for bladder cancer therapy.
噻唑烷二酮（TZD）疗法用于II型糖尿病患者已被证明有助于降低血糖水平。然而，最近的研究表明，可能存在相关的潜在健康问题，包括患膀胱癌的风险以及心血管系统并发症。TZD是核受体PPAR的配体，其激活会导致脂质摄取和胰岛素敏感性增加，这两个过程对于身体无法有效利用胰岛素的糖尿病患者来说都是关键过程。多项研究表明，PPAR/TZD可降低IGF-1水平，从而抑制胰腺癌、结肠癌、肝癌和前列腺癌等癌症的生长。然而，其他研究揭示了该受体作为尿路上皮癌生物标志物的潜力，特别是因为它对膀胱癌细胞迁移有刺激作用。此外，PPAR可能通过从头合成膀胱癌发展所需的营养物质来提供促肿瘤微环境。在本综述中，我们密切研究了TZD类药物及其在患者研究中对PPAR的影响，以及其他作为正调节剂的分子因素，如蛋白磷酸酶5（PP5），这可能对膀胱癌治疗有重要意义。
