内皮素系统在前列腺癌中的研究进展

Endothelin axis in prostate cancer

内皮素(endothelin,ET)、ET受体(endothelin receptor,ETR)及与之相关的信号转导途径统称为内皮素系统,该系统参与了促有丝分裂、抑制细胞凋亡、促进新生血管形成、骨骼重塑、肿瘤侵袭、肿瘤免疫调节、上皮-间质细胞间转换、肿瘤局部侵犯与远处转移等前列腺癌病程中的各个阶段,在前列腺癌的发生、发展及转移中起着重要作用。此外,目前已有一些针对内皮素系统的前列腺癌靶向治疗手段或与其他前列腺癌治疗手段联合应用的研究,并取得良好效果。文中对内皮素系统在前列腺癌中的相关研究及临床应用的进展进行综述,为针对内皮素-1的前列腺癌靶向治疗和联合其它分子靶向治疗提供理论依据。

The endothelin axis,comprising endothelins,endothelin receptors and the endothelin signal transduction pathway,plays an important role in the pathogenesis,development and metastasis of prostate cancer by regulating mitogenesis,cell survival,angiogenesis,bone remodeling,stimulation of the nociceptor receptor,tumor-infiltrating immune cells,epithelial-mesenchymal transition,and tumor invasion and metastatic dissemination.This review highlights the key signaling pathways activated by the endothelin-1 axis in cancer,for an insight into the full spectrum activated by endothelin-1 is critical for the optimal design of targeted therapies.Preliminary experimental and clinical data demonstrate that interfering with endothelin receptors by using endothlin-1 receptor antagonists alone and in combination with cytotoxic drugs or molecular inhibitors could represent a new mechanism-based antitumor strategy.