机构地区:[1]State Key Laboratory of Chemo/Bio-Sensing and Chemometrics,College of Biology,College of Chemistry and Chemical Engineering,Molecular Science and Biomedicine Laboratory and Aptamer Engineering Center of Hunan Province,Hunan University,Changsha,Hunan,410082,China [2]Shenzhen Research Institute,Hunan University,Shenzhen,Guangdong,518000,China [3]Institute of Cancer and Basic Medicine,Chinese Academy of Sciences,The Cancer Hospital of the University of Chinese Academy of Sciences,Hangzhou,Zhejiang,310022,China [4]Department of Neurosurgery and Neuroscience Institute,Baylor Scott&White Health,Temple,TX,76508,USA [5]Texas A&M University Colleges of Medicine and Pharmacy,College Station,TX,77843,USA [6]LIVESTRONG Cancer Institutes and Department of Oncology,Dell Medical School,The University of Texas at Austin,Austin,TX,78712,USA [7]Institute of Molecular Medicine,Renji Hospital,Shanghai Jiao Tong University School of Medicine,And College of Chemistry and Chemical Engineering,Shanghai Jiao Tong University,Shanghai,200240,China
出 处:《Bioactive Materials》2022年第6期278-291,共14页生物活性材料(英文)
基 金:supported by the National Natural Science Foundation of China(No.31701249,31970692,81803068,91953000,21827811);Changsha Science and Technology Plan(kq2004009);Corbett Estate Fund for Cancer Research;the Hunan Provincial Key Area R&D Program(2019SK2201);Hunan Science and Technology Creative Program(2017XK2103);the National Key R&D Program of China(2020YFA0909000).
摘 要:Fibrosarcoma is a serious malignant mesenchymal tumor with strong invasiveness,high recurrence,and poor prognosis.Currently,surgical resection is the main treatment for fibrosarcoma.However,due to the lack of specific biomarkers,the inability to accurately diagnose fibrosarcoma can lead to sub-optimal surgical outcomes and decreased survival.Here,we seek to address this translational barrier and we show that DNA aptamer S11e was able to recognize fibrosarcoma cells(HT1080)but not human embryonic lung fibroblast cells with Kd values in the nanomolar range.In addition,we found that S11e discerned tumors in HT1080 xenograft mouse models and tumor tissues from fibrosarcoma patients.Furthermore,we demonstrated that S11e internalized into HT1080 cells independent of the lysosome pathway and located in mitochondria.Moreover,we revealed that S11e promoted the apoptosis of HT1080 cells and inhibited HT1080 cell migration.Finally,we investigated the biologically functional cellular target of S11e using a mass spectrometry approach,and identified that Diablo/SMAC protein is a cellular binding protein of S11e,by interacting to which S11e inhibited HT1080 cell migration and invasion.Taken together,these results provide the evidence that S11e may be useful for early diagnosis,targeted therapy,and prognostication of fibrosarcoma.
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