He Wenjing, Li Junhe
Institute of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Prostate. 2018 Nov;78(15):1125-1133. doi: 10.1002/pros.23687. Epub 2018 Jul 15.
Exendin-4, one of the most widely used antidiabetic drugs, has recently been reported to have potential antitumor effects in cancers. Prostate cancer (PC) is one of the most common cancers in male patients with type 2 diabetes mellitus, and radiotherapy plays a vital role in the therapy of PC. Whether exendin-4 has the potential to enhance PC response to ionizing radiation (IR) remains unknown. We aimed to explore whether exendin-4 radiosensitizes PC cells.
GLP-1 receptor (GLP-1R) expression in PC tissue samples and cell lines were analyzed, Human prostate cancer cells (PC3 and LNCap) were treated with IR and exendin-4, and subjected to proliferation, clone formation, cell cycle, immunoblotting, and immunohistochemical analysis. An in situ prostate tumor of animal model was established.
We found that GLP-1R was expressed in human PC tissues and cell lines. 1-100 nM exendin-4 promoted the anti-proliferation effects of IR in vitro and in vivo, and enhanced radiation-induced G2/M cycle arrest in PC cells in a dose-dependent manner. Furthermore, Ex-4 increased AMPK phosphorylation, decrease the levels of p-mTOR, cyclin B, and p34 .
Our study suggested exendin-4 radiosensitizes PC cells via activation of AMPK A and subsequent inhibition of p-mTOR, cyclin B, and p34cdc2 activation.
艾塞那肽-4是最广泛使用的抗糖尿病药物之一，最近有报道称其在癌症中具有潜在的抗肿瘤作用。前列腺癌（PC）是2型糖尿病男性患者中最常见的癌症之一，放疗在PC治疗中起着至关重要的作用。艾塞那肽-4是否有可能增强PC对电离辐射（IR）的反应尚不清楚。我们旨在探讨艾塞那肽-4是否能使PC细胞对放疗增敏。
分析PC组织样本和细胞系中胰高血糖素样肽-1受体（GLP-1R）的表达，用人前列腺癌细胞（PC3和LNCap）进行IR和艾塞那肽-4处理，并进行增殖、克隆形成、细胞周期、免疫印迹和免疫组化分析。建立动物模型的原位前列腺肿瘤。
我们发现GLP-1R在人PC组织和细胞系中表达。1-100 nM艾塞那肽-4在体外和体内均促进了IR的抗增殖作用，并以剂量依赖的方式增强了PC细胞中辐射诱导的G2/M期阻滞。此外，Ex-4增加了AMPK磷酸化，降低了p-mTOR、细胞周期蛋白B和p34的水平。
我们的研究表明，艾塞那肽-4通过激活AMPK A并随后抑制p-mTOR、细胞周期蛋白B和p34cdc2激活使PC细胞对放疗增敏。
