文章基本信息

标题：Tigecycline as a dual inhibitor of retinoblastoma and angiogenesis via inducing mitochondrial dysfunctions and oxidative damage
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作者：Ying Xiong ; Wei Liu ; Qian Huang 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：11747
DOI：10.1038/s41598-018-29938-x
语种：English
出版社：Springer Nature
摘要：Retinoblastoma is the most common intraocular malignancy in children with poor prognosis. The progression of retinoblastoma is dependent on a robust angiogenic response. Targeting both retinoblastoma cells and angiogenesis may therefore provide an alternative therapeutic strategy in retinoblastoma. Here, we demonstrated the inhibitory effects of tigecycline, a FDA-approved antibiotic, in retinoblastoma and angiogenesis in vitro and in vivo. We showed that tigecycline significantly inhibited growth and induced caspase-dependent apoptosis of multiple retinoblastoma cell lines. Tigecycline also effectively inhibited angiogenesis through suppressing capillary network formation, migration, proliferation and survival of human retinal microvascular endothelial cell (HREC). Mechanistically, tigecycline acts on both retinoblastoma cells and HREC via inhibiting mitochondrial protein translation, resulting in mitochondrial dysfunction, energy crisis, and oxidative damage. Importantly, we demonstrated the in vivo efficacy of tigecycline in inhibiting retinoblastoma and angiogenesis, and inducing oxidative stress on xenograft mouse model. In addition, ATP levels and growth rates were largely affected in retinoblastoma ρ0 cells that lacked mitochondrial respiration. Our work provides systematic pre-clinical evidence for repurposing tigecycline from its traditional use for retinoblastoma treatment. Our work demonstrates the essential roles of mitochondrial metabolism in both retinoblastoma and its angiogenesis.