title: 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.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University School of Medicine, Taoyuan 333, Taiwan R.O.C.
authors.forename: Hsien-Ming
authors.initials: HM
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University School of Medicine, Taoyuan 333, Taiwan R.O.C.
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University School of Medicine, Taoyuan 333, Taiwan R.O.C.
authors.forename: Angel
authors.initials: A
authors.lastname: Chao
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University School of Medicine, Taoyuan 333, Taiwan R.O.C.
authors.forename: Hung-Hsueh
authors.initials: HH
authors.lastname: Chou
authors.affiliation: Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia V6H3V5, Canada.
authors.forename: Peter C K
authors.initials: PC
authors.lastname: Leung
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University School of Medicine, Taoyuan 333, Taiwan R.O.C.
authors.forename: Hsin-Shih
authors.initials: HS
authors.lastname: Wang
mesh_terms: D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D017337:Sermorelin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; C050361:CDH2 protein, human; D015820:Cadherins; C550121: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)-; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D017337:Sermorelin; D013007:Growth Hormone-Releasing Hormone
keywords: GHRH antagonist; N-cadherin; endometrial cancer; invasion; twist