Objective To investigate the effect of lidocaine on the chemotherapy sensitivity of gastric cancer cells by regulating the Wnt/β-catenin axis. Methods Human gastric cancer cells SGC-7901 in logarithmic growth phase were inoculated into 96-well plates and treated with different concentrations of lidocaine (0, 10, 50, 100, 150, 200 μmol/L) for 24 h. The cell viability at different concentrations was compared. The SGC-7901 cells in logarithmic growth phase were divided into control group, cisplatin group, low concentration lidocaine group (Lido-L group), medium concentration lidocaine group (Lido-M group), high concentration lidocaine group (Lido-H group), high concentration lidocaine + Wnt/β-catenin signal pathway activator SKL2001 group (Lido-H+SKL2001 group). The cell proliferation, invasion, and migration abilities of each group were compared by 5-acetylidene-2'deoxyuracil nucleoside (EdU) cell proliferation detection, Transwell assay, and scratch healing experiment. The apoptosis of each group was detected by TUNEL assay. The expressions of apoptosis, epithelial-mesenchymal transition, and Wnt/β-catenin pathway-related proteins in each group were detected. Results Compared with 0 μmol/L lidocaine, the cell viability of SGC-7901 cells treated with 50, 100, 150, and 200 μmol/L lidocaine was reduced (P < 0.05). Compared with the control group, the EdU positive rate, the number of cell invasion, scratch healing rate, and expressions of vimentin, N-cadherin, B-cell lymphoma-associated protein-2 (Bcl-2), cyclin D1, scattered protein 2 (DVL2), Wnt family member 3a (Wnt3a), β-catenin (β-catenin) were reduced in the cisplatin group, while the cell apoptosis rate was increased, the expressions of E-cadherin, B-cell lymphoma-2-associated X protein (Bax), Cleaved-caspase-3 were increased, and the differences were statistically significant (P < 0.05). Compared with the cisplatin group, the EdU positive rate, the number of cell invasion, scratch healing rate, and expressions of vimentin, N-cadherin, Bcl-2, cyclin Dl, DVL2, Wnt3a, β-catenin were gradually reduced in the Lido-L group, Lido-M group, and Lido-H group, while the cell apoptosis rate, the expressions of E-cadherin, B-cell lymphoma-2-associated X protein (Bax), Cleaved-caspase-3 were increased (P < 0.05). Compared with the Lido-H group, the EdU positive rate, the number of cell invasion, scratch healing rate, and expressions of vimentin, N-cadherin, Bcl-2, cyclin Dl, DVL2, Wnt3a, β-catenin were increased in the Lido-H+SKL2001 group, while the cell apoptosis rate and expressions of E-cadherin, Bax, Cleaved-caspase-3 were reduced, the differences were statistically significant (P < 0.05). Conclusion Lidocaine may enhance the chemotherapy sensitivity of gastric cancer cells by inhibiting the activation of the Wnt/β-catenin axis.

Objective To evaluate the role and potential mechanism of interleukin (IL)-18/IL-18 binding protein (BP) in mediating the killing effect of natural killer (NK)-92MI cells upon endothelial cells from α-1, 3- galactosyltransferase gene-knockout (GTKO) porcine models. Methods NK-92MI cells were divided into the NK, NK+IL-18, NK+GTKO, IL-18+NK+GTKO and IL-18+IL-18BP+NK+GTKO groups. The messenger ribonucleic acid (mRNA) levels of inflammation-related genes in NK-92MI cells were detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The killing effect of NK-92MI cells on endothelial cells from GTKO porcine models was evaluated by lactate dehydrogenase (LDH) assay. The apoptosis of endothelial cells from GTKO porcine models was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The expression levels of proteins with killing effect and apoptosis-related proteins were determined by Western blot. Results Compared with the NK, NK+IL-18 and NK+GTKO groups, the expression levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-8, IL-3, IL-6 and granulocyte-macrophage colony stimulating factor (GM-CSF) mRNA were up-regulated in NK-92MI cells in the IL-18+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Compared with the IL-18+NK+GTKO group, the expression levels of IFN-γ, TNF-α, IL-8, IL-3, IL-6 and GM-CSF mRNA were down-regulated in NK-92MI cells in the IL-18+IL-18BP+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Compared with the NK+GTKO group, the expression levels of perforin, granzyme B and IFN-γ proteins in NK-92MI cells were up-regulated, the killing rate of NK-92MI cells against endothelial cells from GTKO porcine models was enhanced, the apoptosis rate of endothelial cells from GTKO porcine models was increased, and the ratios of B cell lymphoma-2 (Bcl-2)-associated X protein (Bax)/Bcl-2 and cleaved Caspase-3/Caspase-3 in endothelial cells from GTKO porcine models were elevated in the IL-18+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Compared with the IL-18+NK+GTKO group, the expression levels of perforin, granzyme B and IFN-γ proteins were down-regulated, the killing rate of NK-92MI cells against endothelial cells from GTKO porcine models was decreased, the apoptosis rate of endothelial cells from GTKO porcine models was decreased, and the ratios of Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 in endothelial cells from GTKO porcine models were declined in the IL-18+IL-18BP+NK+GTKO group, and the differences were statistically significant (all P < 0.05). Conclusions IL-18BP may block the expression of inflammation-related genes in NK-92MI cells induced by IL-18 and the killing effect of NK-92MI cells on endothelial cells from GTKO porcine models.