Expression of SIRT1 protein in gastric cancer and its relationship with P-gp and Top-Ⅱ alpha / 中国现代普通外科进展

ABSTRACT

Objective:Explore the expression of SIRT1 protein in gastric cancer tissues and cells.Analyze the correlation of SIRT1 protein expression and multidrug resistance protein P-gp and Top-Ⅱ alpha.Methods:Immunohistochemical to detect SIRT1,P-gp and Top-Ⅱ alpha protein in 15 cases of gastric cancer tissue and 15 cases of normal gastric mucosa tissues.Western blot test the expression of SIRT1 protein in normal gastric mucosa epithelial cell line GES-1 and human gastric cancer cell line SGC7901,MKN45,MKN28,HGC27,AGS and MGC803.Western blot test the expression of SIRT1,P-gp and Top-Ⅱ alpha protein in normal gastric mucosa epithelial cell line GES-1 and human gastric cancer cell line SGC7901,MKN45.After siRNA-SIRT1/liposome transfection gastric cancer cells SGC7901,western blot test the changes of expression of SIRT1,P-gp and Top-Ⅱ alpha protein and MTT test the changes of SGC7901 cells proliferation in vitro and the sensitivity of chemotherapy drugs 5-Fu.Results:In 15 cases of gastric cancer tissue have the positive expression of 15 cases of SIRT1 protein,13 cases of P-gp protein and 3 cases of Top-Ⅱ alpha protein.In 15 cases of normal gastric mucosa tissues have the positive expression of 6 cases of SIRT1 protein,5 cases of P-gp protein and 0 cases of Top-Ⅱ alpha protein.The relative quantity of SIRT1 protein expression average were 0.385,0.827,0.009,0.232,0.275,0.159,0.275 in GES-1,SGC7901,MKN45,MKN28,HGC27,AGS and MGC803,respectively.The relative quantity of P-gp protein expression average were 0.339,0.526,1.03 in GES 1,SGC7901 and MKN45 and Top-Ⅱ alpha protein were 0.093,0.889,and 0.158,respectively,siRNA-SIRT1 transfected SGC7901 for 8 hours and after 72 hours to test the relative quantity of SIRT1 protein expression average were 0.965,0.937,0.958,0.567,0.253,0.083 in control,BC-V,negative,siRNA-1,2,3 SIRT1,P-gp were 1.893,1.905,1.932,0.465,0.006,0.465 and Top-Ⅱ alpha were 0.09,0.07,0.073,0.085,0.168,0.085.MTT results showed that after SIRT1 protein expression was inhibited the SGC7901 proliferation has no obvious change in vitro and cell sensitivity to the chemotherapy drugs 5-Fu was increased significantly.Conclusion:SIRT1 expression in gastric cancer tissues and the expression of SIRT1 in gastric cancer tissue and cell carcinoma factors role,SIRT1 protein overexpression can promote P-gp protein expression lower Top-Ⅱ alpha protein expression in gastric cancer cells to chemotherapy of multiple drug resistance increase.