Itraconazole Inhibits AKT/mTOR Signaling and Proliferation in Endometrial Cancer Cells.
Itraconazole Inhibits AKT/mTOR Signaling and Proliferation in Endometrial Cancer Cells.
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DOI：
10.21873/anticanres.11343
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发表时间：
2017-02
影响因子：
2
通讯作者：
H. Tsubamoto;Kayo Inoue;K. Sakata;T. Ueda;R. Takeyama;H. Shibahara;T. Sonoda
中科院分区：
文献类型：
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作者：
H. Tsubamoto;Kayo Inoue;K. Sakata;T. Ueda;R. Takeyama;H. Shibahara;T. Sonoda
背景伊曲康唑是一种常见的抗真菌药物，在临床前和临床研究中已证明具有抗癌活性。本研究调查了伊曲康唑是否对子宫内膜癌 (EC) 细胞发挥这种作用。材料和方法使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物测定法评估细胞活力，并分别通过微阵列分析和免疫印迹评估五种 EC 细胞系的基因和蛋白质表达。结果 伊曲康唑抑制 AN3-CA、HEC-1A 和 Ishikawa 细胞的增殖 (p<0.05)，但不抑制 HEC-50B 或 SNG-II 细胞的增殖。伊曲康唑不会抑制 GLI1 或 GLI2 转录，但会抑制 AN3-CA 和 HEC-1A 细胞中哺乳动物雷帕霉素靶蛋白 (mTOR) 信号成分的表达，同时诱导微管相关蛋白 1A/1B-轻链 3-II（自噬标记物）的表达。 ATP 结合盒转运蛋白 A1 基因在 Ishikawa、HEC-50B 和 SNG-II 细胞中下调。结论 伊曲康唑治疗通过抑制 AKT/mTOR 信号传导来抑制 EC 细胞的生长。
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.