抗真菌药物伊曲康唑通过抑制 Hedgehog 通路在口腔鳞状细胞癌中发挥抗癌作用。
Anti-fungal drug itraconazole exerts anti-cancer effects in oral squamous cell carcinoma via suppressing Hedgehog pathway.
机构信息
Department of Clinical Trial, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, PR China.
Animal Experiment Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China.
出版信息
Life Sci. 2020 Aug 1;254:117695. doi: 10.1016/j.lfs.2020.117695. Epub 2020 May 11.
AIMS
To investigate the therapeutic potential of itraconazole in oral squamous cell carcinoma (OSCC) and its molecular mechanism.
MATERIALS AND METHODS
The in vitro anti-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. The in vivo therapeutic efficacy of itraconazole was assessed by OSCC patient-derived xenograft (PDX) model. Western blot was performed to explore the anti-cancer mechanism.
KEY FINDINGS
Itraconazole 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).
SIGNIFICANCE
Itraconazole showed anti-cancer effects on OSCC via inhibiting the Hedgehog pathway.
目的
研究伊曲康唑治疗口腔鳞状细胞癌（OSCC）的潜力及其分子机制。
材料和方法
通过 CCK-8 法和集落形成实验测定伊曲康唑的体外抗癌作用。Transwell 和划痕愈合实验用于检测细胞侵袭和迁移。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 探索抗癌机制。
主要发现
伊曲康唑呈时间和浓度依赖性抑制 OSCC 细胞的增殖和集落形成；诱导细胞周期停滞和细胞凋亡，并抑制细胞侵袭和迁移。在 OSCC PDX 模型中，伊曲康唑抑制肿瘤生长，降低 Ki-67 表达并诱导细胞凋亡。伊曲康唑下调 Hedgehog 通路的蛋白表达，抑制口腔鳞状细胞癌细胞的增殖和迁移，重组人 sonic hedgehog 蛋白（rSHH）可对其进行修正。
意义
伊曲康唑通过抑制 Hedgehog 通路对 OSCC 表现出抗癌作用。
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