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.

Objective : To investigate the expression of miR-27a in colorectal cancer cell , and to analyze the effect of its targeted regulation of ( Secreted Frizzled Related Protein , SFRP1) on the biological behavior of colorectal cancer cells . Methods : Real time fluorescent quantitative PCR(qRT-PCR) was employed to examine the expres sion of miR-27a and SFRP1 mRNA in colorectal cancer tissues and adjacent normal tissues . Western blot was used to detect the expression of SFRP1 protein in colorectal cancer tissues and adjacent normal tissues . TargetScan soft ware and dual luciferase reporter gene test were used to detect the targeted regulation of miR-27a on SFRP1 . HCT116 cells were transfected with miR-27a mimic , miR-27a inhibitor and negtive control (NC) . The expression of miR-27a and SFRP1 mRNA in each group was determined by qRT-PCR . MTT colorimetry was performed to eval uate the proliferation of each group cells . Transwell assay was used to evaluate the cell invasion and migration ability . Meanwhile , the protein expression levels of SFRP1 , key factors Wnt4 and β-catenin in the Wnt/β catenin signaling pathway were determined by Western blot. Results : Compared with adjacent normal tissues , miR-27a was highly expressed in colorectal cancer tissues , while SFRP1 was low expressed in colorectal cancer tissues ( P < 0.05) . Target Scan software and dual luciferase reporter gene test showed that miR-27a targeted SFRP1 . Compared with NC group , the expression of miR-27a of miR-27a mimic group increased , the proliferation , invasion and migration ability enhanced , the expression of SFRP1 protein decreased , while Wnt4 and β-catenin protein expression increased ( P < 0.05 ) . Compared with miR-27a mimic group , the expression of miR-27a of miR-27a inhibitor group decreased , the proliferation , invasion and migration ability reduced , the expression of SFRP1 protein in creased , while Wnt4 and β-catenin protein expression decreased( P < 0.05) . Conclusion miR-27a can target SFRP1 , inhibit the proliferation , invasion and migration of colorectal cancer cells , mainly by up regulating SFRP1 and blocking the downstream Wnt/β-catenin signaling pathway , which provides a new direction for clinical treatment.