利用探针跳跃式扫描离子电导显微镜技术揭示结直肠癌单细胞层面对H_(2)O_(2)良性应激的动态响应  

Exploration of individual colorectal cancer cell responses to H_(2)O_(2)eustress using hopping probe scanning ion conductance microscopy

作　　者：王东 Emily Woodcock 杨羲 Hiromi Nishikawa Elena V.Sviderskaya Masanobu Oshima Christopher Edwards 张彦军 Yuri Korchev Dong Wang;Emily Woodcock;Xi Yang;Hiromi Nishikawa;Elena V.Sviderskaya;Masanobu Oshima;Christopher Edwards;Yanjun Zhang;Yuri Korchev(WPI Nano Life Science Institute(WPI-Nano LSI),Kanazawa University,Kanazawa 920-1192,Japan;Department of Medicine,Imperial College London,London W120NN,United Kingdom;Cell Biology Research Centre,Molecular and Clinical Sciences Research Institute,St George’s,University of London,London SW170RE,United Kingdom)

机构地区：[1]WPI Nano Life Science Institute(WPI-Nano LSI),Kanazawa University,Kanazawa 920-1192,Japan [2]Department of Medicine,Imperial College London,London W120NN,United Kingdom [3]Cell Biology Research Centre,Molecular and Clinical Sciences Research Institute,St George’s,University of London,London SW170RE,United Kingdom

出　　处：《Science Bulletin》2024年第12期1909-1919,共11页科学通报（英文版）

基　　金：supported by Japan Society for the Promotion of Science KAKENHI(21H01770,22K04890);the World Premier International Research Center Initiative(WPI),MEXT,Japan。

摘　　要：Colorectal cancer(CRC),a widespread malignancy,is closely associated with tumor microenvironmental hydrogen peroxide(H_(2)O_(2))levels.Some clinical trials targeting H_(2)O_(2)for cancer treatment have revealed its paradoxical role as a promoter of cancer progression.Investigating the dynamics of cancer cell H_(2)O_(2)eustress at the single–cell level is crucial.In this study,non–contact hopping probe mode scanning ion conductance microscopy(HPICM)with high-sensitive Pt–functionalized nanoelectrodes was employed to measure dynamic extracellular to intracellular H_(2)O_(2)gradients in individual colorectal cancer Caco–2cells.We explored the relationship between cellular mechanical properties and H_(2)O_(2)gradients.Exposure to 0.1 or 1 mmol/L H_(2)O_(2)eustress increased the extracellular to intracellular H_(2)O_(2)gradient from 0.3 to 1.91 or 3.04,respectively.Notably,cellular F–actin–dependent stiffness increased at 0.1 mmol/L but decreased at 1 mmol/L H_(2)O_(2)eustress.This H_(2)O_(2)–induced stiffness modulated AKT activation positively and glutathione peroxidase 2(GPX2)expression negatively.Our findings unveil the failure of some H_(2)O_(2)-targeted therapies due to their ineffectiveness in generating H_(2)O_(2),which instead acts eustress to promote cancer cell survival.This research also reveals the complex interplay between physical properties and biochemical signaling in cancer cells'antioxidant defense,illuminating the exploitation of H_(2)O_(2)eustress for survival at the single–cell level.Inhibiting GPX and/or catalase(CAT)enhances the cytotoxic activity of H_(2)O_(2)eustress against CRC cells,which holds significant promise for developing innovative therapies targeting cancer and other H_(2)O_(2)-related inflammatory diseases.

关 键 词：SPM NANOPROBE NANOBIOLOGY SECM ROS STIFFNESS 

分 类 号：R735.3[医药卫生—肿瘤]