Expression Of Adipokin Chemerin In Endometrioid Adenocarcinoma And Its Effect On Proliferation And Invasion Of Ishikawa Cells

Endometrial carcinomas(EC)have a high incidence of malignant tumors in the female reproductive system in China,only second to cervical cancer.At present,Endometrioid Adenocarcinoma is the most common type of histology.Most patients have a good prognosis,while there are still some patients who have found it to be late,which is not effective for general treatment methods such as surgery and radiotherapy and chemotherapy.Therefore,it is necessary to find new treatment methods for endometrioid adenocarcinoma.As we know,high estrogen level is one of its risk factors,which is mostly related to metabolic syndrome,obesity,and diabetes.In recent years,studies have found that the occurrence and development of tumors are closely related to the disorder of lipid metabolism,and at the same time,they have opened up new treatment methods for the treatment of tumors.It is reported that the adipose tissue secreted by adipose tissue can participate in the regulation of cell growth,proliferation,differentiation,apoptosis,etc.,thereby regulating tumor growth.Chemerin is one of the newly discovered adipokines.It can regulate the differentiation of preadipocytes into adipocytes,increase the blood supply of adipose tissue and participate in the regulation of metabolic processes,and it can also play its pro-inflammatory role by stimulating the migration of dendritic cells,macrophages,NK cells and neutrophils.Some studies have shown that chemerin has a strong correlation with the occurrence and development of tumors,and has been reported in the research of liver cancer,adrenal cancer,prostate cancer,non-small cell lung cancer and other diseases.Scholars have found that chemerin is significantly increased in peripheral blood of patients with endometrial carcinoma,while there is little report on whether chemerin is related to the occurrence and development of endometrioid adenocarcinoma.Objective:The purpose of this study was to investigate the adipokine chemerin with the occurrence and development of endometrioid adenocarcinoma and to explore the potential mechanisms between them.Materials and Methods:In this study,immunohistochemical SP method was used to detect the expression of chemerin in endometrioid adenocarcinoma tissue,atypical proliferative endometrial tissue and normal proliferative endometrium tissue.qRT-PCR was used to detect chemerin expression in endometrioid adenocarcinoma tissue and normal endometrial tissue adjacent to cancer.Different concentrations of exogenous recombinant human chemerin protein at different times was detected on highly differentiated endometrioid adenocarcinoma ishikawa cell lines.Cell proliferation was detected by the CCK8 method.After selecting the optimal concentration,the scratch test,transwell method,and flow cytometry death detection method and plate cloning experiment were used to detect the effects of chemerin on the migration,invasion,apoptosis and tumorigenicity of Ishikawa cells.The Western Blot method was used to detect the changes of related proteins,and to explore the possible mechanism of chemerin on Iishikawa cells.Results:1.Immunohistochemical results suggest that the expression of chemerin in endometrioid adenocarcinoma tissue and atypical hyperplasia endometrium tissue is significantly higher than that in normal proliferative endometrium tissue,and the positive rate in the highly differentiated endometrioid adenocarcinoma group is significantly higher than that in the moderately differentiated and poorly differentiated groups,the expression of chemerin in endometrial tissues of patients with lymph node metastasis and late stage was significantly higher than that of patients without lymph node metastasis and early stage,the difference was statistically significant.2.In vitro cell experiments,the proliferation of Ishikawa cells after treatment with recombinant human chemerin protein was significantly higher than that of the blank group,and the proliferation rate increased with time.In 72h and 96h,there was no significant difference in the proliferation rate between the same group of cells,and 72h was selected as the optimal time of action.In the four groups of cell culture,the cell proliferation rates of 50ng/ml and 100ng/ml were significantly lower than those of 150ng/ml group,but the three groups were significantly higher than the blank group(P<0.05).150ng/ml was selected as the optimal concentration for subsequent experiments..3.48 hours and 72 hours later,the migration rate and the number of invaded cells in the blank group were significantly lower than those in the chemerin group(P<0.05);4.48 hours and 72 hours later,there was no significant difference in the apoptosis rate between the blank group and the chemerin group(P>0.05);.5.After 14 days,the colony formation rate in the chemerin group was significantly higher than that in the blank group(P<0.05);6.The content of phosphorylated p38MAPK protein and MMP-9 protein in the chemerin group was significantly higher than that in the blank group(P<0.05).Conclusion:The expression of chemerin is increased in endometrioid adenocarcinoma tissues and is associated with lymph node metastasis and clinical stage.Chemerin may promote the proliferation and invasion of Ishikawa cells by activating the p38MAPK pathway and increasing MMP-9 protein.