Research On The Expression And Mechanism Of Succinate Dehydrogenase B In The Endometrial Carcinoma Cells

Purpose:To observe the expression of succinate dehydrogenase B(SDHB)in endometrial carcinoma tissues and cell lines(Ishikawa and RL95-2 cells).The effects of succinic acid(succinate),the corresponding catalytic enzyme SDHB,and their receptor GPR91 on the proliferation and invasion of endometrial carcinoma cell lines(Ishikawa and RL95-2 cells)were then investigated,and the expression and mechanism of SDHB and its metabolite succinic acid in endometrial carcinoma were elucidated.Methods: First,the expression of SDHB,GLUT4 and GPR91 protein in endometrial carcinoma from patient and normal endometrium tissue from control women was detected by immunohistochemistry.Then,we used 0mmol/L,2.5mmol/L,5mmol/L,7.5mmol/L,10mmol/L,15mmol/L,or 20mmol/L DMS to treat endometrial carcinoma cell lines(Ishikawa and RL95-2 cells)in vitro,after 24 h,cell proliferation and Matrigel invasion assay were used to detect the proliferation and invasion ability of these cells.The expression levels of SDHB,GLUT4 and GPR91 proteins were detected by western blotting assay.Then,we used estrogen and high glucose medium to treat these cancer cell lines in vitro,and detected the expression of GLUT4,GPR91 and estrogen receptor protein by western blotting assay.Cell proliferation and Matrigel invasion assay were used to detect the proliferation and invasiveness of the cells.Finally,we constructed the tumor bearing mice in vivo to confirm the results above.Result: DMS significantly promoted the proliferation and invasion ability of endometrial carcinoma Ishikawa and RL95-2 cells in vitro,and showed a dose-dependent manner,and the difference was statistically significant(P<0.05).After SDHB overexpression or GPR91 silencing,the proliferation and invasion ability of endometrial carcinoma Ishikawa and RL95-2 cells were decreased,and the difference was statistically significant(P<0.05).Estrogen and high glucose could promote the proliferation and invasion of Ishikawa and RL95-2 cells in vitro,and promote the expression of GLUT4 and GPR91.In addition,the high glucose treatment could promote the expression of estrogen receptor in Ishikawa and RL95-2 cells,and the difference was statistically significant(P<0.05).Animal experiments showed that SDHB inhibited the growth of endometrial carcinoma of mice.Conclusion: Compared with normal endometrium,endometrial cancer patients have high expression of GLUT4 and GPR91,but low expression of SDHB.Succinic acid can promote the proliferation and invasion of endometrial cancer cells,and up-regulate the expression of GLUT4 and GPR91 in these cells.High glucose up-regulates the expression of estrogen receptor.Animal experiments showed that succinic acid promotes the proliferation and growth of endometrial carcinoma.On the contrary,tumor growth was inhibited after SDHB overexpression.