Adiponectin Inhibites The Growth Of Endometrial Cancer Cells And Activates The Signaling Pathway

Endometrial cancer is the most common female malignancy in Europe and the United States.In China,endometrial cancer is one of the three major gynecological malignancies after cervical cancer.In recent years,the incidence of endometrial cancer has gradually become younger.Our previous research shows that low adiponectin level is an independent risk factor for endometrial cancer.The positive expression rate of AdipoR1 in endometrial adenocarcinoma was significantly lower than that in normal endometrium,and the expression of AdipoR2 was significantly lower than that of normal endometrium.In endometrial adenocarcinoma tissues,the low expression of AdipoR1 was significantly associated with FIGO stage,pathological grade,depth of muscle infiltration,lymph node metastasis,and lymphatic vessel involvement.The low expression of AdipoR2 was significantly associated with the degree of tissue differentiation.To further investigate the association between adiponectin and endometrial cancer,two different endometrial cancer cell lines were used in this study to detect adiponectin and pathway inhibitors in response to endometrial cancer cells.Changes in different signaling molecules,expression of apoptosis-related proteins Bcl-2,matrix metalloproteinase-9,and effects on cell growth,proliferation,migration,and apoptosis rate.To further clarify the specific mechanism of adiponectin on the endometrial cancer cells.Objective: To investigate the effects of different concentrations of adiponectin on proliferation of endometrial carcinoma HEC-1B and RL95-2 cells,and to explore the mechanism of adenylate-activated protein kinase(AMPK)signaling pathway,apoptosis-related protein Bcl-2 The changes of matrix metalloproteinase-9(MMP-9)and the effects of adiponectin on migration and apoptosis of endometrial cancer cells.Methods: Different concentrations of adiponectin and pathway inhibitors were used to treat endometrial carcinoma HEC-1B and RL95-2 cells.The proliferation of the two cells was detected.0ug/ml lipid was used.Adriamycin(blank control group),20ug/ml adiponectin(APN group),AMPK pathway inhibitor complex C(complex C group),complex C+20ug/ml adiponectin(complex C+APN group)After 30 min,the expression of Bcl-2 and MMP-9 genes was detected by RT-PCR.Western Blot was used to detect the expression of AdipoR1 and AdipoR2.western blot was used to detect the expression of related proteins of the AMPK pathway,the expression of apoptosis-related proteins Bcl-2 and MMP-9.Transwell assay was used to detect the migration of two cells,and flow cytometry was used to detect the apoptosis rate.Results:(1)Adiponectin concentration> 5ug/ml can significantly inhibit the proliferation of human endometrial cancer cells in a concentration-dependent manner(P<0.05).(2)The expression of AdipoR1 and AdipoR2 was detected in both cells.The protein expression was higher than that of AdipoR2,and the difference was statistically significant(p<0.05).(3)Phosphorylation of AMPK was induced in 20 ug/ml adiponectin for 30 min,and phosphorylation of mTOR and 4EBP1 was inhibited(P<0.05),but no effect on the corresponding total protein;Bcl-2,MMP-9 Protein expression levels decreased(P<0.05).The AMPK pathway inhibitor complex C inhibited the phosphorylation of the above proteins(P<0.05)and blocked Bcl-2 and MMP-9 genes and proteins(P<0.05).(4)Compared with the blank group,the apoptotic rate of adiponectin group increased(P<0.05),and the number of migrating cells decreased(P<0.05).AMPK pathway inhibitor complex C blocked these effects(P<0.05).Conclusion: Adiponectin can inhibit the proliferation of endometrial cancer cells through AMPK signaling pathway;inhibit the migration of endometrial cancer cells and induce apoptosis.