title: Expression of Hedgehog Signals and Growth Inhibition by Itraconazole in Endometrial Cancer.
abstract: BACKGROUND
  There exist limited therapeutic opportunities for the treatment of endometrial cancer (EC). Itraconazole, a common anti-fungal agent and a potent inhibitor of the Hedgehog pathway, has been shown to be clinically effective for various types of cancers, but its clinical efficacy for EC is unknown. Herein, we evaluated the efficacy of itraconazole in treating EC.
  
  
  METHODS
  We performed immunohistochemistry on EC tumour samples including serous endometrial intraepithelial carcinoma (SEIC). We further evaluated the in vitro efficacy of itraconazole for inhibiting proliferation and migration of EC cell lines.
  
  
  RESULTS
  Sonic Hedgehog and glioma-associated oncogene homolog 1 (GLI1) were expressed in SEIC and endometrioid adenocarcinoma. We found that itraconazole significantly inhibited tumour cell growth in both dose-dependent and time-dependent manners and inhibited migration of HEC-1A cells.
  
  
  CONCLUSIONS
  Hedgehog signaling plays a role in carcinogenesis and malignant progression in EC. Itraconazole at a physiological dose may suppress progression of EC.
authors.affiliation: Department of Obstetrics and Gynecology, Hyogo College of Medicine, Mukogawa, Nishinomiya, Hyogo, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Obstetrics and Gynecology, Hyogo College of Medicine, Mukogawa, Nishinomiya, Hyogo, Japan Department of Medical Oncology, Meiwa Hospital, Agenaruo, Nishinomiya, Hyogo, Japan tsuba@hyo-med.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsubamoto
authors.affiliation: Department of Obstetrics and Gynecology, Hyogo College of Medicine, Mukogawa, Nishinomiya, Hyogo, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Sakata
authors.affiliation: Department of Obstetrics and Gynecology, Hyogo College of Medicine, Mukogawa, Nishinomiya, Hyogo, Japan.
authors.forename: Riya
authors.initials: R
authors.lastname: Sakane
authors.affiliation: Department of Surgical Pathology, Hyogo College of Medicine, Mukogawa, Nishinomiya, Hyogo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hao
authors.affiliation: Department of Surgical Pathology, Hyogo College of Medicine, Mukogawa, Nishinomiya, Hyogo, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Hirota
authors.affiliation: Department of Medical Oncology, Meiwa Hospital, Agenaruo, Nishinomiya, Hyogo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sonoda
authors.affiliation: Department of Obstetrics and Gynecology, Hyogo College of Medicine, Mukogawa, Nishinomiya, Hyogo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shibahara
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D018269:Carcinoma, Endometrioid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017964:Itraconazole / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
chemical_list: D000970:Antineoplastic Agents; C400551:GLI1 protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D017964:Itraconazole
keywords: Itraconazole; endometrial cancer; hedgehog