Itraconazole Inhibits AKT/mTOR Signaling and Proliferation in Endometrial Cancer Cells.
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.



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.



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.



Itraconazole treatment suppresses the growth of EC cells by inhibiting AKT/mTOR signalling.
Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan tsuba@hyo-med.ac.jp.|Department of Medical Oncology, Meiwa Hospital, Nishinomiya, Japan.
Hiroshi
H
Tsubamoto
Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan.
Kayo
K
Inoue
Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan.
Kazuko
K
Sakata
Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan.
Tomoko
T
Ueda
Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan.
Ryu
R
Takeyama
Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan.
Hiroaki
H
Shibahara
Department of Medical Oncology, Meiwa Hospital, Nishinomiya, Japan.
Takashi
T
Sonoda
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology*; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D017964:Itraconazole; C546842:MTOR protein, human; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases
AKT/mTOR; Itraconazole; autophagy; endometrial cancer; hedgehog