Role And Mechanism Of KLF11 In The Formation Of 5-fluorouracil Resistance By Regulating EMT In Gastric Cancer Cells

Objective: To investigate the role and mechanism of KLF11 in5-Fluorouracil resistance in gastric cancer cells through regulating tumor EMT.Methods: Gastric cancer tissues,adjacent normal tissues,normal human gastric epithelial cells and gastric cancer cell lines,quantitative real-time polymerase chain reaction(qPCR),Western blot,and immunohistochemistry were used to detect the expression of KLF11,Selecting highly expressed human gastric cancer cell line to inhibit KLF11 expression in cells by RNA interference,Detecting the Sensitivity of Different Groups to 5-Fu,Detection of multidrug resistance-related genes and EMT marker mRNA and protein expression in cells.To elucidate the expression of KLF11 in gastric cancer and human gastric cancer cell lines,Sensitivity of human gastric cancer cell line BGC823 to 5-Fu after transfection with KLF11-siRNA-2,To investigate the mechanism of 5-Fu resistance,the relationship between KLF11,EMT and multidrug resistance-related genes,To provide experimental and theoretical basis for improving the 5-Fu resistance of gastric cancer and finding new therapeutic targets.Results:1.The expression of KLF11 in gastric cancer tissues was significantly higher than that in paracancerous tissues.2.The expression of KLF11 in gastric cancer cell line MKN28,gastric cancer cell line SGC7901 and gastric cancer cell line BGC823 was significantly higher than that of normal gastric mucosal epithelial cells GES-1.3.The sensitivity of human gastric cancer cell line BGC823 transfected with KLF11-siRNA-2 to 5-Fu was significantly higher than that of negativecontrol.4.The expression of P-gp,GST-?,LRP,MRP and TS in human gastric cancer cell line BGC823 transfected with KLF11-siRNA-2 was down-regulated.The expressions of N-cadherin,Vimentin and ?-catenin were down-regulated while the expression of E-cadherin was up-regulated.Conclusion:1.The expression of KLF11 in gastric cancer tissues was significantly higher than that in adjacent normal tissues,and KLF11 was highly expressed in gastric cancer.2.The expression of KLF11 in gastric cancer cell lines was significantly higher than that in normal gastric epithelial cells GES-1,and KLF11 was highly expressed in gastric cancer cell line BGC823.3.Inhibition of KLF11-expressing gastric cancer cell line BGC823down-regulated the expression of N-cadherin,Vimentin and ?-catenin,and increased the expression of E-cadherin.KLF11 may be involved in the EMT of gastric cancer cell line BGC823.4.Inhibition of KLF11 expression increased the sensitivity of gastric cancer cell line BGC823 to 5-Fu,and KLF11 may be a novel gene involved in gastric cancer cell line BGC823 5-Fu.5.The expression of P-gp,GST-?,LRP,MRP and TS in KLF11-expressing human gastric cancer cell line BGC823 was down-regulated.