伊曲康唑调节刺猬信号通路、WNT/β-连环蛋白信号通路以及Akt信号通路，并抑制宫颈癌细胞的增殖。

Itraconazole Modulates Hedgehog, WNT/β-catenin, as well as Akt Signalling, and Inhibits Proliferation of Cervical Cancer Cells.

作者信息

Ueda Tomoko, Tsubamoto Hiroshi, Inoue Kayo, Sakata Kazuko, Shibahara Hiroaki, Sonoda Takashi

机构信息

Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan.

Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan

出版信息

Anticancer Res. 2017 Jul;37(7):3521-3526. doi: 10.21873/anticanres.11720.

DOI:10.21873/anticanres.11720

PMID:28668841

Abstract

BACKGROUND/AIM: Repurposing itraconazole as an anticancer agent has been evaluated in several studies. The present study investigated whether itraconazole exerts an anticancer effect on cervical cancer cells.

MATERIALS AND METHODS

CaSki and HeLa cells were cultured in itraconazole and vehicle after which colony-forming and cell viability assays were performed. Transcription and protein expression were assessed by cDNA microarray analysis and immunoblotting, respectively.

RESULTS

Itraconazole suppressed proliferation of CaSki and HeLa cells in a dose- and time-dependent manner. Furthermore, CaSki cells were more significantly affected by itraconazole than HeLa cells. The microarray analysis showed an 8-fold down-regulation in the expression of GLI1, WNT4 and WNT10A among itraconazole-treated CaSki cells. Moreover, the transcription of sterol carrier protein-2 and ATP-binding cassette transporter-1 was unaffected by itraconazole. Immunoblots showed suppression in β-catenin expression and Akt phosphorylation.

CONCLUSION

Itraconazole is a multi-targeting anticancer agent and a promising therapeutic agent for cervical cancer.

摘要

背景/目的：在多项研究中已对将伊曲康唑重新用作抗癌药物进行了评估。本研究调查了伊曲康唑是否对宫颈癌细胞具有抗癌作用。

材料与方法

将CaSki和HeLa细胞在伊曲康唑和赋形剂中培养，之后进行集落形成和细胞活力测定。分别通过cDNA微阵列分析和免疫印迹评估转录和蛋白质表达。

结果

伊曲康唑以剂量和时间依赖性方式抑制CaSki和HeLa细胞的增殖。此外，CaSki细胞比HeLa细胞受伊曲康唑的影响更显著。微阵列分析显示，在经伊曲康唑处理的CaSki细胞中，GLI1、WNT4和WNT10A的表达下调了8倍。此外，固醇载体蛋白2和ATP结合盒转运体1的转录不受伊曲康唑影响。免疫印迹显示β-连环蛋白表达和Akt磷酸化受到抑制。