Wu Hsien-Ming, Huang Hong-Yuan, Schally Andrew V, Chao Angel, Chou Hung-Hsueh, Leung Peter C K, Wang Hsin-Shih
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University School of Medicine, Taoyuan 333, Taiwan R.O.C.
Veterans Affairs Medical Center and Departments of Pathology and Medicine, Division of Hematology/Oncology, University of Miami Miller School of Medicine, Miami, FL 33125, USA.
Oncotarget. 2017 Jan 17;8(3):4410-4421. doi: 10.18632/oncotarget.13877.
More than 25% of patients diagnosed with endometrial carcinoma have invasive primary cancer accompanied by metastases. Growth hormone-releasing hormone (GHRH) plays an important role in reproduction. Here, we examined the effect of a GHRH antagonist on the motility of endometrial cancer cells and the mechanisms of action of the antagonist in endometrial cancer. Western blotting and immunohistochemistry (IHC) were used to determine the expression of the GHRH receptor protein. The activity of Twist and N-cadherin was determined by Western blotting. Cell motility was assessed by an invasion and migration assay. GHRH receptor siRNA was applied to knockdown the GHRH receptor in endometrial cancer cells. The GHRH antagonist inhibited cell motility in a dose-dependent manner. The GHRH antagonist inhibited cell motility and suppressed the expression of Twist and N-cadherin, and the suppression was abolished by GHRH receptor siRNA pretreatment. Moreover, the inhibition of Twist and N-cadherin with Twist siRNA and N-cadherin siRNA, respectively, suppressed cell motility. Our study indicates that the GHRH antagonist inhibited the cell motility of endometrial cancer cells through the GHRH receptor via the suppression of Twist and N-cadherin. Our findings represent a new concept in the mechanism of GHRH antagonist-suppressed cell motility in endometrial cancer cells and suggest the possibility of exploring GHRH antagonists as potential therapeutics for the treatment of human endometrial cancer.
超过25%被诊断为子宫内膜癌的患者患有伴有转移的浸润性原发性癌症。生长激素释放激素（GHRH）在生殖过程中发挥着重要作用。在此，我们研究了一种GHRH拮抗剂对子宫内膜癌细胞运动性的影响以及该拮抗剂在子宫内膜癌中的作用机制。采用蛋白质免疫印迹法和免疫组织化学（IHC）来测定GHRH受体蛋白的表达。通过蛋白质免疫印迹法测定Twist和N-钙黏蛋白的活性。通过侵袭和迁移试验评估细胞运动性。应用GHRH受体小干扰RNA（siRNA）敲低子宫内膜癌细胞中的GHRH受体。GHRH拮抗剂以剂量依赖的方式抑制细胞运动性。GHRH拮抗剂抑制细胞运动性并抑制Twist和N-钙黏蛋白的表达，而GHRH受体siRNA预处理可消除这种抑制作用。此外，分别用Twist siRNA和N-钙黏蛋白siRNA抑制Twist和N-钙黏蛋白可抑制细胞运动性。我们的研究表明，GHRH拮抗剂通过GHRH受体抑制子宫内膜癌细胞的运动性，其机制是抑制Twist和N-钙黏蛋白。我们的研究结果代表了GHRH拮抗剂抑制子宫内膜癌细胞运动性机制的一个新概念，并提示探索GHRH拮抗剂作为治疗人类子宫内膜癌潜在疗法的可能性。
