PMID- 28179296 OWN - NLM STAT- MEDLINE DCOM- 20170213 LR - 20211204 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 37 IP - 2 DP - 2017 Feb TI - Itraconazole Inhibits AKT/mTOR Signaling and Proliferation in Endometrial Cancer Cells. PG - 515-519 AB - BACKGROUND: Itraconazole is a common antifungal agent that has demonstrated anticancer activity in preclinical and clinical studies. This study investigated whether itraconazole exerts this effect in endometrial cancer (EC) cells. MATERIALS AND METHODS: Cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and gene and protein expression were assessed by microarray analysis and immunoblotting, respectively, in five EC cell lines. RESULTS: Itraconazole-suppressed proliferation of AN3-CA, HEC-1A and Ishikawa cells (p<0.05) but not of HEC-50B or SNG-II cells. Itraconazole did not suppress GLI1 or GLI2 transcription but did inhibit the expression of mammalian target of rapamycin (mTOR) signaling components in AN3-CA and HEC-1A cells, while inducing that of microtubule-associated protein 1A/1B-light chain 3-II, a marker of autophagy. ATP-binding cassette transporter A1 gene was down-regulated in Ishikawa, HEC-50B and SNG-II cells. CONCLUSION: Itraconazole treatment suppresses the growth of EC cells by inhibiting AKT/mTOR signalling. CI - Copyright(c) 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. FAU - Tsubamoto, Hiroshi AU - Tsubamoto H AD - Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan tsuba@hyo-med.ac.jp. AD - Department of Medical Oncology, Meiwa Hospital, Nishinomiya, Japan. FAU - Inoue, Kayo AU - Inoue K AD - Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Sakata, Kazuko AU - Sakata K AD - Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Ueda, Tomoko AU - Ueda T AD - Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Takeyama, Ryu AU - Takeyama R AD - Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Shibahara, Hiroaki AU - Shibahara H AD - Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Sonoda, Takashi AU - Sonoda T AD - Department of Medical Oncology, Meiwa Hospital, Nishinomiya, Japan. LA - eng PT - Journal Article PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 304NUG5GF4 (Itraconazole) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Oncogene Protein v-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Dose-Response Relationship, Drug MH - Endometrial Neoplasms/*drug therapy/genetics/metabolism/pathology MH - Female MH - Gene Expression/drug effects MH - Humans MH - Itraconazole/*pharmacology MH - Oncogene Protein v-akt/*antagonists & inhibitors/metabolism MH - Signal Transduction/drug effects MH - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism OTO - NOTNLM OT - AKT/mTOR OT - Itraconazole OT - autophagy OT - endometrial cancer OT - hedgehog EDAT- 2017/02/10 06:00 MHDA- 2017/02/14 06:00 CRDT- 2017/02/10 06:00 PHST- 2016/11/12 00:00 [received] PHST- 2016/12/20 00:00 [revised] PHST- 2016/12/22 00:00 [accepted] PHST- 2017/02/10 06:00 [entrez] PHST- 2017/02/10 06:00 [pubmed] PHST- 2017/02/14 06:00 [medline] AID - 37/2/515 [pii] AID - 10.21873/anticanres.11343 [doi] PST - ppublish SO - Anticancer Res. 2017 Feb;37(2):515-519. doi: 10.21873/anticanres.11343.