Kayo Inoue1, Hiroshi Tsubamoto2, Kazuko Sakata1, Riya Sakane1, Hiroyuki Hao3, Seiichi Hirota3, Takashi Sonoda4, Hiroaki Shibahara1. 1. Department of Obstetrics and Gynecology, Hyogo College of Medicine, Mukogawa, Nishinomiya, Hyogo, Japan. 2. 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. 3. Department of Surgical Pathology, Hyogo College of Medicine, Mukogawa, Nishinomiya, Hyogo, Japan. 4. Department of Medical Oncology, Meiwa Hospital, Agenaruo, Nishinomiya, Hyogo, Japan.
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. MATERIALS AND 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. CONCLUSION: Hedgehog signaling plays a role in carcinogenesis and malignant progression in EC. Itraconazole at a physiological dose may suppress progression of EC. Copyright
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. MATERIALS AND 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. CONCLUSION: Hedgehog signaling plays a role in carcinogenesis and malignant progression in EC. Itraconazole at a physiological dose may suppress progression of EC. Copyright
Authors: Thiago S Lima; Luciano O Souza; Diego Iglesias-Gato; Johanna Elversang; Flemming Steen Jørgensen; Tuula Kallunki; Martin A Røder; Klaus Brasso; José M A Moreira Journal: Front Pharmacol Date: 2022-06-03 Impact factor: 5.988