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纳米金棒重塑肿瘤细胞能量代谢并阻遏肿瘤转移
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摘要
纳米金棒在生物医学领域可用于多模式成像、药物输运、光热治疗等,其对肿瘤转移的效果尚不明确。本工作发现纳米金棒可在体外有效抑制肿瘤细胞的迁移及侵袭。通过整合系统生物学的研究手段,我们发现纳米金棒可显著下调能量代谢相关基因的表达,从而抑制肿瘤细胞的氧化磷酸化,并致使糖酵解速率代偿性地升高。氧化磷酸化的下调导致胞内ATP含量下降、肌动蛋白组装受抑制,使肿瘤细胞的运动能力显著受限。纳米金棒还在裸鼠体内显示出阻遏肿瘤转移的效果。这些研究结果提示纳米金棒有望在肿瘤的治疗中发挥重要作用。
Gold nanostructures have received much attention because of their distinct physicochemical properties. However, little is known regarding their effect on tumor metastasis. In the present investigation, we show that gold nanorods(AuN Rs) effectively inhibit their migration and invasion in vitro. Quantitative proteomics and real-time PCR array analyses indicate that exposure of cells to AuN Rs can down-regulate the expression of diverse energy generation-related genes, which accounts for their inhibition of mitochondrial oxidative phosphorylation(OXPHOS) and glycolysis. The impairment of OXPHOS and glycolysis resulted in a distinctive reduction of ATP production and subsequent inhibition of F-actin cytoskeletal assembly, which is crucial for the migration and invasion of cancer cells. The inhibitory effect of AuN Rs on cancer cell migration was also confirmed in vivo. Taken together, the unique mechanism in inhibiting cancer cell migration by Au NRs might provide a new approach to specific cancer therapeutic treatment.
引文
[1]Teng Zhou,Meifang Yu,Bo Zhang,Liming Wang,Xiaochun Wu,Hejiang Zhou,Yipeng Du,Junfeng Hao,Yaping Tu,Chunying Chen and Taotao Wei.Inhibition of cancer cell migration by gold nanorods:molecular mechanisms and implications for cancer therapy.Advanced Functional Materials 24(2014),6922-6932.
    [2]Teng Zhou,Bo Zhang,Peng Wei,Yipeng Du,Hejiang Zhou,Meifang Yu,Liang Yan,Wendi Zhang,Guangjun Nie,Chunying Chen,Yaping Tu and Taotao Wei.Energy metabolism analysis reveals the mechanism of inhibition of breast cancer cell metastasis by PEG-modified graphene oxide nanosheets.Biomaterials 35(2014),9833-9843.
    [3]Hejiang Zhou,Bo Zhang,Jiajia Zheng,Meifang Yu,Teng Zhou,Kai Zhao,Yanxia Jia,Xingfa Gao,Chunying Chen and Taotao Wei.The inhibition of migration and invasion of cancer cells by graphene via the impairment of mitochondrial respiration.Biomaterials 35(2014),1597-1607.

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