Oncotarget

Research Papers:

Growth hormone-releasing hormone antagonist inhibits the invasiveness of human endometrial cancer cells by down-regulating twist and N-cadherin expression

Hsien-Ming Wu, Hong-Yuan Huang, Andrew V. Schally, Angel Chao, Hung-Hsueh Chou, Peter C.K. Leung, Hsin-Shih Wang _

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Oncotarget. 2017; 8:4410-4421. https://doi.org/10.18632/oncotarget.13877

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Abstract

Hsien-Ming Wu1, Hong-Yuan Huang1, Andrew V. Schally3, Angel Chao1, Hung-Hsueh Chou1, Peter C.K. Leung2, Hsin-Shih Wang1

1Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University School of Medicine, Taoyuan, Taiwan R.O.C. 333

2Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada V6H3V5

3Veterans Affairs Medical Center and Departments of Pathology and Medicine, Division of Hematology/Oncology, University of Miami Miller School of Medicine, Miami, FL 33125, USA

Correspondence to:

Hsien-Ming Wu, email: danielwu@cgmh.org.tw

Hsin-Shih Wang, email: hswang@cgmh.org.tw

Keywords: GHRH antagonist, endometrial cancer, invasion, twist, N-cadherin

Received: August 23, 2016     Accepted: December 01, 2016     Published: December 10, 2016

ABSTRACT

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.


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