透明质酸钠修饰过氧化钙纳米粒子诱导胃癌细胞焦亡

田仪督; 高生宝; 贡克文; 何瑛珏; 李洋; 步雪峰

doi:10.16016/j.2097-0927.202310061

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透明质酸钠修饰过氧化钙纳米粒子诱导胃癌细胞焦亡

基础医学 | 更新时间：2026-01-09

- 透明质酸钠修饰过氧化钙纳米粒子诱导胃癌细胞焦亡
- Sodium-hyaluronate-modified calcium peroxide nanoparticles induce pyroptosis in gastric cancer cells in vitro
- 陆军军医大学学报 2024年46卷第13期页码：1535-1544
- 作者机构：
  
  1.212000 江苏镇江，江苏大学附属人民医院普外科
  2.212000 江苏镇江，江苏大学附属人民医院呼吸内科
- 作者简介：
  
  [ 步雪峰，E-mail：xuefengbu05@163.com BU Xuefeng, E-mail: xuefengbu05@163.com
- 基金信息：
  
  镇江市科技创新资金项目(SH2023004)
- DOI：10.16016/j.2097-0927.202310061
  中图分类号： R730.23;R735.2;R914.2
- 收稿：2023-10-17，
  
  修回：2023-12-26，
  
  纸质出版：2024-07-15
- 稿件说明：
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田仪督, 高生宝, 贡克文, 等. 透明质酸钠修饰过氧化钙纳米粒子诱导胃癌细胞焦亡[J]. 陆军军医大学学报, 2024,46(13):1535-1544.

Yidu TIAN, Shengbao GAO, Kewen GONG, et al. Sodium-hyaluronate-modified calcium peroxide nanoparticles induce pyroptosis in gastric cancer cells in vitro[J]. Journal of Army Medical University, 2024, 46(13): 1535-1544.
田仪督, 高生宝, 贡克文, 等. 透明质酸钠修饰过氧化钙纳米粒子诱导胃癌细胞焦亡[J]. 陆军军医大学学报, 2024,46(13):1535-1544. DOI： 10.16016/j.2097-0927.202310061.

Yidu TIAN, Shengbao GAO, Kewen GONG, et al. Sodium-hyaluronate-modified calcium peroxide nanoparticles induce pyroptosis in gastric cancer cells in vitro[J]. Journal of Army Medical University, 2024, 46(13): 1535-1544. DOI： 10.16016/j.2097-0927.202310061.

摘要

目的

探讨透明质酸钠修饰过氧化钙纳米粒子(sodium-hyaluronate-modified calcium oxide nanoparticles，SH-CaO

NPs)诱导人胃癌细胞焦亡的作用及其可能机制。

方法

运用透射电镜(transmission electron microscope，TEM)、X射线衍射(X-ray diffraction，XRD)、红外光谱及Zeta电位观测SH-CaO

NPs的合成情况；细胞划痕实验验证SH-CaO

NPs对人胃癌细胞迁移能力的影响；CCK-8法检测SH-CaO

NPs对胃癌细胞增殖活性的影响以及使用Nod样受体

蛋白3(NOD-like receptor protein 3，NLRP3)、半胱氨酸天冬氨酸蛋白酶1(cysteinyl aspartate specific proteinase，Caspase-1)抑制剂预处理后胃癌细胞的增殖活性；DCFH-DA荧光探针及流式细胞仪检测细胞内活性氧的表达量；免疫荧光法及Western blot检测各组细胞NLRP3、Caspase-1、GSDMD蛋白表达水平。

结果

TEM、XRD、红外光谱及Zeta电位观测结果提示SH-CaO

NPs成功制备。CCK-8法及细胞划痕实验显示，SH-CaO

NPs作用于人胃癌细胞24 h后，胃癌细胞生长明显受到抑制(

＜0.001)。ROS荧光及流式细胞仪结果显示，SH-CaO

NPs作用于人胃癌细胞24 h后肿瘤细胞内ROS含量升高(

＜0.001)，予以ROS抑制剂(NAC)后细胞内NLRP3蛋白含量升高，Caspase-1、GSDMD剪切体即活性片段表达量上升(

0.001)，予以NLRP3、Caspase-1抑制剂可逆转此过程。

结论

SH-CaO

NPs可抑制人胃癌细胞活力，可能通过激活ROS/NLRP3/Caspase-1/GSDMD信号通路介导炎症反应和细胞焦亡。

Abstract

Objective

To investigate the role of sodium-hyaluronate-modified calcium peroxide nanoparticles (SH-CaO

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-CaO

NPs. Cell scratch assay and CCK-8 assay were employed to observe the impacts of SH-CaO

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-CaO

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-CaO

NPs. Cell scratch assay and CCK-8 assay showed that application of SH-CaO

NPs for 24 h significantly inhibited the proliferation of HGC-27 cells (

0.001)

while

CLSM and flow cytometry indicated the treatment also promoted the production of ROS (

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 (

0.001)

while pretreatment of both NLRP3 inhibitor and Caspase-1 inhibitor could reverse the process.

Conclusion

SH-CaO

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.

关键词

Keywords

references

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