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:
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.
Sodium-hyaluronate-modified calcium peroxide nanoparticles induce pyroptosis in gastric cancer cells in vitro
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
2
NPs的合成情况;细胞划痕实验验证SH-CaO
2
NPs对人胃癌细胞迁移能力的影响;CCK-8法检测SH-CaO
2
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。
To investigate the role of sodium-hyaluronate-modified calcium peroxide nanoparticles (SH-CaO
2
NPs) in inducing pyroptosis in human gastric cancer cells and its possible mechanisms.
Methods
2
Transmission electron microscopy (TEM)
X-ray diffraction (XRD)
infrared spectroscopy
and zeta potential test were used to confirm the synthesis of SH-CaO
2
NPs. Cell scratch assay and CCK-8 assay were employed to observe the impacts of SH-CaO
2
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
2
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
2
TEM images
XRD
infrared spectroscopy
and zeta potential test confirmed
the successful preparation of SH-CaO
2
NPs. Cell scratch assay and CCK-8 assay showed that application of SH-CaO
2
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
2
SH-CaO
2
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
AJANI J A, D'AMICO T A, BENTREM D J, et al . Gastric cancer, Version 2.2022, NCCN clinical practice guidelines in oncology[J ] . J Natl Compr Canc Netw, 2022, 20(2): 167-192. DOI: 10.6004/jnccn.2022.0008.
MACHLOWSKA J, BAJ J, SITARZ M, et al . Gastric cancer: epidemiology, risk factors, classification, genomic characteristics and treatment strategies[J ] . Int J Mol Sci, 2020, 21(11): 4012. DOI: 10.3390/ijms21114012.
MONACK D M, RAUPACH B, HROMOCKYJ A E, et al . Salmonella typhimurium invasion induces apoptosis in infected macrophages[J ] . Proc Natl Acad Sci U S A, 1996, 93(18): 9833-9838. DOI: 10.1073/pnas.93.18.9833..
SHI J J, ZHAO Y, WANG Y P, et al . Inflammatory caspases are innate immune receptors for intracellular LPS[J ] . Nature, 2014 , 514(7521): 187-192. DOI: 10.1038/nature13683.
SWANSON K V, DENG M, TING J P Y. The NLRP3 inflammasome: molecular activation and regulation to therapeutics[J]. Nat Rev Immunol, 2019, 19(8): 477-489. DOI: 10.1038/s41577-019-0165-0.
BURDETTE B E, ESPARZA A N, ZHU H, et al . Gasdermin D in pyroptosis[J ] . Acta Pharm Sin B, 2021, 11(9): 2768-2782. DOI: 10.1016/j.apsb.2021.02.006.
YANG Y, LIU P Y, BAO W, et al . Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway[J ] . BMC Cancer, 2020, 20(1): 28. DOI: 10.1186/s12885-019-6491-6.
GONG Q, XIE H J, SHUANG W B. Research progress in effect of cell pyrosis on tumor progression[J]. China Med Eng, 2022, 30(8): 54-57. DOI: 10.19338/j.issn.1672-2019.2022.08.011.
FU Y L, L UO Y H, FANG G, et al . Research progress on biological role of pyrolysis in gastric cancer[J ] . Chin J Clin Oncol, 2022, 49(6): 314-318. DOI: 10.12354/j.issn.1000-8179.2022.20210784.
NAGARAJU G P, SRIVANI G, DARIYA B, et al . Nanoparticles guided drug delivery and imaging in gastric cancer[J ] . Semin Cancer Biol, 2021, 69: 69-76. DOI: 10.1016/j.semcancer.2020.01.006.
HU Y P, WANG X C, ZHAO P, et al . Nanozyme-catalyzed oxygen release from calcium peroxide nanoparticles for accelerated hypoxia relief and image-guided super-efficient photodynamic therapy[J ] . Biomater Sci, 2020, 8(10): 2931-2938. DOI: 10.1039/D0BM00187B.
TANG Q Y, DU L, LIU P F. Nanoparticle-mediated diagnosis and treatment of gastric cancer[J]. Tumor, 2022, 42(7): 518-524. DOI: 10.3781/j.issn.1000-7431.2022.2108-0552.
ZHANG M, SONG R X, LIU Y Y, et al . Calcium-overload-mediated tumor therapy by calcium peroxide nanoparticles[J ] . Chem, 2019, 5(8): 2171-2182. DOI: 10.1016/j.chempr.2019.06.003.
SMYTH E C, NILSSON M, GRABSCH H I, et al . Gastric cancer[J ] . Lancet, 2020, 396(10251): 635-648. DOI: 10.1016/s0140-6736(20)31288-5.
JOSHI S S, BADGWELL B D. Current treatment and recent progress in gastric cancer[J]. CA A Cancer J Clin, 2021, 71(3): 264-279. DOI: 10.3322/caac.21657.
YANG F, LI A M, LIU H, et al . Gastric cancer combination therapy: synthesis of a hyaluronic acid and cisplatin containing lipid prodrug coloaded with sorafenib in a nanoparticulate system to exhibit enhanced anticancer efficacy and reduced toxicity[J ] . Drug Des Dev Ther, 2018, 12: 3321-3333. DOI: 10.2147/dDDT.s176879.
DING B B, CHEN H, TAN J, et al . ZIF-8 nanoparticles evoke pyroptosis for high-efficiency cancer immunotherapy[J ] . Angew Chem Int Ed, 2023, 62(10): e202215307. DOI: 10.1002/anie.202215307.
BERGSBAKEN T, FINK S L, COOKSON B T. Pyroptosis: host cell death and inflammation[J]. Nat Rev Microbiol, 2009, 7(2): 99-109. DOI: 10.1038/nrmicro2070.
LIU L H, ZHANG Y H, QIU W X, et al . Dual-s tage light amplified photodynamic therapy against hypoxic tumor based on an O 2 self-sufficient nanoplatform[J ] . Small, 2017, 13(37): 1-9. DOI: 10.1002/smll.201701621..
MARTÍN MATEO M C, MARTÍN B, SANTOS BENEIT M, et al . Catalase activity in erythrocytes from colon and gastric cancer patients. Influence of nickel, lead, mercury, and cadmium[J ] . Biol Trace Elem Res, 1997, 57(1): 79-90. DOI: 10.1007/BF02803872.
WANG F H, LIANG Q Q, MA Y X, et al . Silica nanoparticles induce pyroptosis and cardiac hypertrophy via ROS/NLRP3/Caspase-1 pathway[J ] . Free Radic Biol Med, 2022, 182: 171-181. DOI: 10.1016/j.freeradbiomed.2022.02.027.
XU K, CHANG M Q, WANG Z Y, et al . Multienzyme-mimicking LaCoO 3 nanotrigger for programming cancer-cell pyroptosis[J ] . Adv Mater, 2023, 35(35): e2302961. DOI: 10.1002/adma.202302961..
PERILLO B, DI DONATO M, PEZONE A, et al . ROS in cancer therapy: the bright side of the moon[J ] . Exp Mol Med, 2020, 52 (2): 192-203. DOI:10.1038/s12276-020-0384-2.
Oxaliplatin suppresses gastric cancer by inducing cuproptosis
Effects of LncRNA FGD5-AS1 on migration and invasion of gastric cancer cells by regulating miR-302b-3p/E2F1 axis
Related Author
LIU Zhenkun
PENG Ziyi
XIANG Junyu
WANG Bin
JIANG Baishan
QIU Qiu
LI Yuhong
PENG Ziyi
Related Institution
Department of Gastroenterology, Hechuan District People’s Hospital
Frontier Science Center for Immunology and Metabolism, School of Pharmaceutical Sciences, Wuhan University
Department of Gastroenterology, Chongqing Key Laboratory of Precise Prevention and Treatment of Digestive Malignancies, Daping Hospital, Army Medical University(Third Military Medical University)
Department of Cell Biology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University)
Department of Gastroenterology, Chongqing Hechuan People’s Hospital