Impact of lidocaine on the chemotherapy sensitivity of gastric cancer cells via regulating Wnt/β-catenin axis
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 concen-trations of lidocaine(0,10,50,100,150,200 μmol/L)for 24 h.The cell viability at different con-centrations 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 lido-caine 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'de-oxyuracil nucleoside(EdU)cell proliferation detection,Transwell assay,and scratch healing experi-ment.The apoptosis of each group was detected by TUNEL assay.The expressions of apoptosis,epi-thelial-mesenchymal transition,and Wnt/β-catenin pathway-related proteins in each group were detec-ted.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 vimen-tin,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 statisti-cally 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 vimen-tin,N-cadherin,Bcl-2,cyclin D1,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.
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