Objective To investigate the effect of docosahexaenoic acid(DHA)on human colon cancer cell line HT-29 and underlying mechanism.Methods Human colon cancer cell line HT-29 was incubated with DMSO(control),DHA(25,50,100 μmol/L)and 100 μmol/L DHA and/or 30 μmol/L 740Y-P.Proliferation was examined by MITT;apoptosis was detected by annexin V-FITC/PI.Western blot was used for detection of protein expression of Bcl-2,Bax apoptosis-related protein and PI3K/Akt/mTOR pathway,and RT-qPCR was used for checking mRNA expression of NLRP3/Caspase-1/IL-1β pathway.Results Compared with the control group,DHA 25,50,and 100 μmol/L treatment of HT-29 cells resulted in decreased cell survival(P＜0.05),increased apoptosis(P＜0.05),decreased Bcl-2/Bax ratio(P＜0.05)and decreased phosphorylation of PI3K,Akt and mTOR in HT-29 cells(P＜0.05 or P＜0.01).Expressions of NLRP3,Caspase-1 and IL-1 β mRNA were decreased(P＜0.05).In addition,cell viability,protein phos-phorylation(p-PI3K,p-Akt,p-mTOR)and relative mRNA expression of NLRP3,Caspase 1,and IL-1β were lower in HT-29 cells which were co-incubated with DHA 100 μmol/L and 740Y-P 30 μmol/L than those in the control group(P＜0.05 or P＜0.01)and 740Y-P 30 μmol/L group(P＜0.05),while higher than that of DHA 100 μmol/L group(P＜0.05 or P＜0.01).Conclusions DHA inhibits the proliferation of human colon cancer cell line HT-29,its mecha-nism is potentially related to the inhibition of PI3K/Akt/mTOR and NLRP3/Caspase-1/IL-1 β signaling pathways.