Sodium-hyaluronate-modified calcium peroxide nanoparticles induce pyroptosis in gastric cancer cells in vitro
10.16016/j.2097-0927.202310061
- VernacularTitle:透明质酸钠修饰过氧化钙纳米粒子诱导胃癌细胞焦亡
- Author:
Yidu TIAN
1
;
Shengbao GAO
;
Kewen GONG
;
Yingjue HE
;
Yang LI
;
Xuefeng BU
Author Information
1. 212000 江苏镇江,江苏大学附属人民医院普外科
- Keywords:
gastric cancer;
nanoparticles;
pyroptosis;
NOD-like receptor protein 3;
Caspase-1
- From:
Journal of Army Medical University
2024;46(13):1535-1544
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of sodium-hyaluronate-modified calcium peroxide nanoparticles(SH-CaO2 NPs)in inducing pyroptosis in human gastric cancer cells and its possible mechanisms.Methods Transmission electron microscopy(TEM),X-ray diffraction(XRD),infrared spectroscopy,and zeta potential test were used to confirm the synthesis of SH-CaO2 NPs.Cell scratch assay and CCK-8 assay were employed to observe the impacts of SH-CaO2 NPs on the migration and proliferation of human gastric cancer cell line HGC-27.The generation of reactive oxygen species(ROS)was observed with confocal laser scanning microscopy(CLSM)and quantified with flow cytometry in the cells after SH-CaO2 NPs treatment or with pretreatment with ROS inhibitor NAC.Furthermore,the effects of pretreatment of NLRP3 inhibitor(MCC950)and Caspase-1 inhibitor(VX765)on the proliferative activity and on expression of their own and their downstream GSDMD in HGC-27 cells were also investigated with CCK-8 assay,immunofluorescence assay and Western blotting.Results TEM images,XRD,infrared spectroscopy,and zeta potential test confirmed the successful preparation of SH-CaO2 NPs.Cell scratch assay and CCK-8 assay showed that application of SH-CaO2 NPs for 24 h significantly inhibited the proliferation of HGC-27 cells(P<0.001),while,CLSM and flow cytometry indicated the treatment also promoted the production of ROS(P<0.001).Pretreatment of ROS inhibitor NAC resulted in up-regulation of NLRP3,and increased expression levels of cleaved Caspase-1 and N-terminal fragment of GSDMD(P<0.001),while pretreatment of both NLRP3 inhibitor and Caspase-1 inhibitor could reverse the process.Conclusion SH-CaO2 NPs inhibit cell viability of human gastric cancer,which may mediate the inflammatory response and pyroptosis by activating the ROS/NLRP3/Caspase-1/GSDMD signaling pathway.