关键词: 胃癌, 青蒿素, TLR4, NF-κB信号通路, 炎症, 增殖, 凋亡

Abstract: Objective  To investigate whether artemisinin regulates the proliferation,apoptosis and secretion of inflammatory factors in gastric cancer cells through the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway.Methods Gastric cancer AGS cells were divided into control (NC) group,50μmol/L artemisinin group,100μmol/L artemisinin group,200μmol/L artemisinin group,pcDNA+200μmol/L artemisinin group and pcDNA-TLR4+200μmol/L artemisinin group.After the treatment,CCK-8 method was performed to detect cell proliferation activity,flow cytometry was used to measure cell apoptosis,cyclin D1 (CyclinD1),activated cysteine-containing aspartate proteolytic enzyme-3 (Cleaved-caspase-3),TLR4,p-p65,and p65 levels were detected by Western blot.The expression of tumor necrosis factor-α (TNF-α),interleukin (IL)-6 and IL-1β inflammatory factors were tested by enzyme-linked immunosorbent assay (ELISA),and the expression of TLR4 mRNA was detected by RT-qPCR.Results Compared with the NC group,the AGS cell proliferation activity,the expression levels of CyclinD1 protein,TNF-α,IL-6,IL-1β,TLR4 mRNA,TLR4 protein and p-p65/p65 ratio decreased in 50-μmol/L artemisinin group,100μmol/L artemisinin group and 200μmol/L artemisinin group.The apoptosis rate and Cleaved-caspase-3 level increased,and there was a statistically significant difference between the artemisinin group and the NC group at different concentrations (P<0.05).The ratio of p-p65/p65 in AGS cells in the 200 μmol/L artemisinin group was lower than that in the NC group,and the difference was statistically significant (P<0.05).Compared with the pcDNA+200 μmol/L artemisinin group,the expression level of TLR4 mRNA,proliferation activity,the expression level of CyclinD1 protein,TNF-α,IL-6,IL-1β and p-p65/p65 ratio in AGS cells in the pcDNA-TLR4+200 μmol/L artemisinin group increased,the apoptosis rate and the level of Cleaved-caspase-3 decreased,and the difference between the two groups was statistically significant (P<0.05).Conclusion Artemisinin inhibits the proliferation activity and inflammatory factor secretion of gastric cancer cells by down-regulating the TLR4/NF-κB signaling pathway,and promotes apoptosis.

Key words: gastric cancer, artemisinin, TLR4, NF-κB signaling pathway, inflammation, proliferation, apoptosis