The Effect And Mechanism Of KLF11 In Gastric Cancer Cells To Oxaliplatin Resistance

Objective: To study the expression of KLF11 mRNA and protein in human gastric cancer tissue,normal stomach tissue,human gastric cell line MGC803,SGC7901,MKN-45 and gastric epithelial cell line GES-1 to compare oxaliplatin resistance in each group after inhibiting the expression of KLF11 with RNA interference in human gastric cancer cell line MKN-45,to detect the related genes of multidrug resistance,and to discuss the mechanism of KLF11 in gastric cancer cells to oxaliplatin resistance.Methods: Human gastric cancer tissue,normal stomach tissue(distance from cancer margin at least 5 cm),human gastric cancer cell line MGC803,SGC7901,MKN-45 and gastric epithelial cell line GES-1 were selected as the research object,and the KLF11 mRNA and protein were detected by using Rt-PCR and western blot.MKN-45 cells were selected to follow-up experiment for its high expression of KLF11 mRNA and protein.KLF11 specific interference siRNA sequence and its negative control sequence were esigned and synthesized,then they were transfected in different group of MNK-45 cells with different concentration.Then the expression of KLF11 mRNA and protein after 24 h,48h and 72 h were detected with q PCR and western blot.The difference of oxaliplatin resistance in MKN-45 cells was compared that transfected with KLF11-siRNA-2,negative group and blank control group.Apoptosis rate of each group were also compared with flow cytometry,and the expression of survivin,Bcl2,Bax and caspases were detected.Results:1.The expression of KLF11 mRNA and protein in human gastric cancer tissue were significantly higher than that in normal stomach tissue(P<0.05).2.The expression of KLF11 mRNA and protein in human gastric cellline were significantly higher than that in gastric epithelial cell line,and the expressions in MKN-45 cell line were significantly higher than that in other cell line(P<0.05).3.The expression of KLF11 mRNA and protein in Transfection group were significantly higher than that in negative group and blank control group(F=28.027,P<0.05;F=221.881;P<0.05).4.In the MTT assay,there was significant different between the OD570 of transfection group,blank control group and negative control group(P<0.05).5.The expression of survivin and Bcl2 mRNA and protein in Transfection group were significantly lower than that in negative group and blank control group(P<0.05).The expression of Bax,caspase 3,caspase8 and caspase 9 mRNA and protein in transfection group were significantly higher than that in negative group and blank control group(P<0.05).There was not significant different between the expression of caspase 12 in transfection group,blank control group and negative group(P>0.05).Conclusion:1.The expression of KLF11 mRNA and protein were significantly higher in human gastric cancer tissue and cell line.It reveals that KLF11 has closely relationgship with gastric cancer.2.It could significantly increased the sensitivity of MKN-45 cells to L-OHP by inhibiting the expression of KLF11,and KLF11 may participate in the drug resistance of L-OHP in gastric cancer.3.The mechanism of KLF11 in reducing the chemosensitivity of L-OHP in gastric cancer cell may be related to up-regulation of survivin and Bcl2 expression and down-regulation of caspases expression,...