酮康唑在肝细胞癌治疗中的新作用：将 PTGS2 与线粒体自噬机制联系起来。
A novel role for ketoconazole in hepatocellular carcinoma treatment: linking PTGS2 to mitophagy machinery.
机构信息
a Department of Gastrointestinal Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital , Sichuan University, Collaborative Innovation Center for Biotherapy , Chengdu , P.R. China.
b Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine , Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu , P.R. China.
出版信息
Autophagy. 2019 Apr;15(4):733-734. doi: 10.1080/15548627.2019.1569934. Epub 2019 Jan 22.
Ketoconazole is a broad-spectrum antifungal agent, which has recently been characterized as a potential anticancer agent in several cancer types. However, the molecular mechanism underlying the anticancer effect of ketoconazole is not clearly defined. Our recent findings demonstrate that ketoconazole suppresses the growth of hepatocellular carcinoma (HCC) cells by exacerbating mitophagy in vitro and in vivo. Mechanistically, PINK1-PRKN-mediated mitophagy are led by ketoconazole-induced suppression of PTGS2 (prostaglandin-endoperoxide synthase 2), which in turn results in mitochondrial dysfunction and consequent apoptosis. These data link PTGS2 to mitophagy machinery and implicate ketoconazole as a potential therapeutic option for HCC treatment.
酮康唑是一种广谱抗真菌药物，最近在几种癌症类型中被描述为一种潜在的抗癌药物。然而，酮康唑抗癌作用的分子机制尚不清楚。我们最近的研究结果表明，酮康唑通过在体外和体内加剧自噬来抑制肝癌（HCC）细胞的生长。在机制上，酮康唑诱导的前列腺素内过氧化物合酶 2（PTGS2）抑制导致 PINK1-PRKN 介导的自噬，进而导致线粒体功能障碍和随后的细胞凋亡。这些数据将 PTGS2 与自噬机制联系起来，并暗示酮康唑可能是 HCC 治疗的一种潜在治疗选择。
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