Anti -fungal drug itraconazole exerts anti -cancer e ffects in oral squamous cell carcinoma via suppressing Hedgehog pathway
Anti -fungal drug itraconazole exerts anti -cancer e ffects in oral squamous cell carcinoma via suppressing Hedgehog pathway
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DOI：
10.1016/j.lfs.2020.117695
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发表时间：
2020-08-01
期刊：
影响因子：
6.1
通讯作者：
Li, Su
中科院分区：
文献类型：
--
作者：
Ban, Liuxian;Mei, Ting;Li, Su
目的探讨伊曲康唑治疗口腔鳞状细胞癌(OSCC)的潜力及其分子机制。材料与方法采用CCK-8法和集落形成法测定伊曲康唑的体外抗癌作用。 Transwell 和伤口愈合测定用于检查细胞侵袭和迁移。通过 OSCC 患者来源的异种移植（PDX）模型评估伊曲康唑的体内治疗效果。通过Western blot探讨其抗癌机制。 主要发现伊曲康唑以时间和浓度依赖性方式抑制OSCC细胞的增殖和集落形成；诱导细胞周期停滞和凋亡，并抑制细胞侵袭和迁移。在 OSCC PDX 模型中，伊曲康唑阻碍肿瘤生长、降低 Ki-67 表达并诱导细胞凋亡。伊曲康唑下调Hedgehog通路蛋白表达，抑制口腔鳞状细胞癌细胞的增殖和迁移，重组人声刺猬蛋白(rSHH)可以修正这一现象。意义伊曲康唑通过抑制Hedgehog通路对口腔鳞癌发挥抗癌作用。
AimsTo investigate the therapeutic potential of itraconazole in oral squamous cell carcinoma (OSCC) and its molecular mechanism.Materials and methodsThein vitroanti-cancer effects of itraconazole was determined by CCK-8 assay and colony formation assay. Transwell and wound healing assays were used to examine cell invasion and migration. Thein vivotherapeutic efficacy of itraconazole was assessed by OSCC patient-derived xenograft (PDX) model. Western blot was performed to explore the anti-cancer mechanism.Key findingsItraconazole inhibited cell proliferation and colony formation of OSCC cells in a time and concentration dependent manner; induced cell cycle arrest and apoptosis, as well as inhibited cell invasion and migration. In the OSCC PDX model, itraconazole impeded tumor growth, reduced Ki-67 expression and induced apoptosis. Itraconazole downregulated the protein expression of Hedgehog pathway to inhibit proliferation and migration of oral squamous cell carcinoma cells, which can be revised by recombinant human sonic hedgehog protein (rSHH).SignificanceItraconazole showed anti-cancer effects on OSCCviainhibiting the Hedgehog pathway.