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

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.

• Authors: Hsien-Ming Wu, Hong-Yuan Huang, Andrew V Schally, Angel Chao, Hung-Hsueh Chou, Peter C K Leung, Hsin-Shih Wang
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 3 Pg. 4410-4421 (Jan 17 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28032599 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• Antineoplastic Agents
• CDH2 protein, human
• Cadherins
• GHRH(1-29)NH2, (PhAc-Ada)(0)-Tyr(1), Arg(2), Fpa(5,6), Ala(8), Har(9), Tyr(Me)(10), His(11), Orn(12,) Abu(15), His(20), Orn(21), Nle(27), Arg(28), Har(29)-
• Nuclear Proteins
• RNA, Small Interfering
• TWIST1 protein, human
• Twist-Related Protein 1
• Sermorelin
• Growth Hormone-Releasing Hormone

Topics

• Antigens, CD (genetics, metabolism)
• Antineoplastic Agents
• Cadherins (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Down-Regulation
• Endometrial Neoplasms (drug therapy, genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Knockdown Techniques
• Growth Hormone-Releasing Hormone (antagonists & inhibitors, genetics)
• HeLa Cells
• Humans
• Nuclear Proteins (genetics, metabolism)
• RNA, Small Interfering (pharmacology)
• Sermorelin (analogs & derivatives, pharmacology)
• Signal Transduction (drug effects)
• Twist-Related Protein 1 (genetics, metabolism)