Acad Integrated Med & College of Pharmacy, Department of Pharmacy, Dalian Medical University, Dalian, 116044, People's Republic of China.
Department of Plastic and Reconstructive Surgery, The First Bethune Hospital of Jilin University, Chang Chun, 130021, People's Republic of China.
J Cancer Res Clin Oncol. 2020 Feb;146(2):297-304. doi: 10.1007/s00432-019-03117-5. Epub 2020 Jan 20.
Itraconazole is an antifungal drug that has been clinically used for over 30 years. In recent years, scholars have discovered that it possesses an anticancer effect. Moreover, its mechanism has been clarified to some degree. What deserves to be mentioned is that itraconazole acting on the Hedgehog pathway has made a new progress in the treatment of cancers. While interestingly, studies have demonstrated that the Hedgehog pathway is largely activated in different cancer cells.
This review tries to highlight the effect of itraconazole on smoothened receptor (SMO) in the Hedgehog pathway, thereby reducing the glioma-associated oncogene homolog (GLI) release and finally exhibiting a range of anticancer effects, promoting apoptosis of cancer cells, and inhibiting proliferation by indirect inhibition of NF-κB pathway and inflammation, moreover, promoting the expression of cyclin-dependent kinase inhibitors, inhibiting the expression of target genes transcribed by GLI such as BCL-2 and Cyclin-D1. Besides, itraconazole increases the number of Bnip3, subsequently, inducing the dissociation of the Beclin-1/BCL-2 binding complex, as a result of ultimately promoting autophagy of cancer cells.
As a new anticancer drug, whether itraconazole eventually entering clinical application requires the joint eforts of all scholars. In any case, an in-depth study on itraconazole will bring new hope for cancer patients in the near future.
伊曲康唑是一种抗真菌药物，已经在临床上使用了 30 多年。近年来，学者们发现它具有抗癌作用。此外，其作用机制在一定程度上得到了阐明。值得一提的是，伊曲康唑作用于 Hedgehog 通路在癌症治疗方面取得了新的进展。有趣的是，研究表明 Hedgehog 通路在不同的癌细胞中被大量激活。
本综述试图强调伊曲康唑对 Hedgehog 通路中 smoothened 受体（SMO）的作用，从而减少与神经胶质瘤相关的致癌基因同系物（GLI）的释放，最终表现出多种抗癌作用，促进癌细胞凋亡，通过间接抑制 NF-κB 通路和炎症抑制增殖，此外，促进细胞周期蛋白依赖性激酶抑制剂的表达，抑制由 GLI 转录的靶基因如 BCL-2 和 Cyclin-D1 的表达。此外，伊曲康唑增加了 Bnip3 的数量，随后诱导 Beclin-1/BCL-2 结合复合物的解离，最终促进癌细胞自噬。
作为一种新型抗癌药物，伊曲康唑最终是否能进入临床应用需要所有学者的共同努力。无论如何，对伊曲康唑的深入研究将为癌症患者在不久的将来带来新的希望。
