Effects of aspirin-induced GSDME-dependent pyroptosis on the proliferation of colorectal cancer cells
10.19405/j.cnki.issn1000-1492.2023.12.005
- VernacularTitle:阿司匹林诱发GSDME依赖性细胞焦亡对结肠癌细胞增殖的影响
- Author:
Xueqin SIMA
1
;
Yanting SU
;
Chengwu LI
Author Information
1. 湖北科技学院医学部基础医学院组胚教研室,咸宁 437100
- Keywords:
aspirin;
Gasdermin E;
colorectal cancer;
Caco-2 cells;
pyroptosis
- From:
Acta Universitatis Medicinalis Anhui
2023;58(12):2019-2023
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of aspirin-induced Gasdermin E(GSDME)dependent pyroptosis and the related mechanism of colorectal cancer cell proliferation.Methods The colorectal cancer cells Caco2 were cultured in vitro.MTT assay was used to detect the effects of aspirin intervention with different concentrations(1.0,2.5,5.0,10.0,15.0,20.0 mmol/L)on the proliferation activity of colorectal cancer cells.The effect of aspirin intervention on the morphology of colorectal cancer cells was observed under the microscope.Lactate dehy-drogenase(LDH)release assay was used to investigate the effect of aspirin intervention on cell membrane integrity.The protein expression levels of NOD-like receptor protein(NLRP3),cysteinyl aspartate and specific proteinase 1(Caspase-1),Gasdermin E-N(GSDME-N)in colorectal cancer cells were detected by Western blot.The contents of interleukin-1 β(IL-1 β)and interleukin-18(IL-18)in cell supernatant after GSDME silencing were detected by ELISA.After silencing GSDME,cell morphological changes were observed under a microscope,and cell membrane integrity was observed by LDH release assay;The contents of IL-1 β and IL-18 in cell supernatant were determined by ELISA after GSDME silencing.Results MTT results showed that aspirin could decrease the proliferation activi-ty of Caco-2 in a concentration-dependent manner(P<0.01).Morphological observation and LDH experiment showed that aspirin could promote the occurrence of pyroptosis(P<0.05).Western blot showed that aspirin could increase the expression levels of NLRP3,Caspase-1,GSDME-N of pyroptosis-related pathway genes(P<0.05).ELISA showed that aspirin could significantly increase the concentration of IL-1 β and IL-18 in Caco-2 cells(P<0.01).After GSDME silencing,the pyroptosis was significantly inhibited(P<0.05)and the expression of IL-1 βand IL-18 decreased significantly(P<0.01).Conclusion Aspirin can inhibit the proliferation of Caco-2 by indu-cing the pyroptosis of GSDME-dependent cells,thus inhibiting colon cancer.