Effect Of FKBP38 Protein Expression On Endometrial Cancer Cell Proliferation And Invasion Ability And Its Mechanism

Endometrial carcinoma(EC)is a gynecological malignancy derived from endometrial epithelium.Its incidence rate is ranked sixth among women's malignant tumors.Early screening is known to improve the long-term prognosis,and therefore,has always been the focal point in the treatment of endometrial cancer.FK506-binding protein 38(FKBP38)is a member of immunophilin family.It is an endogenous inhibitor of mammalian target of rapamycin(m TOR),which can bind with m TOR to inhibit m TOR activity and regulate downstream signaling.Previous studies of our group found that the expression of FKBP38 protein was decreased in breast cancer and ovarian cancer,indicating that FKBP38 protein may be related to the occurrence and development of tumors.This study will systematically explore the inhibitory effect and mechanisms of FKBP38 on EC cell growth,and potentially provide a new target for the clinical diagnosis and treatment of EC.Objective: This subject aims to study the correlation between the expression levels of FKBP38 protein in EC cells and tumor development,metastasis,and possible mechanisms of action.Methods: Examine the expression levels of FKBP38 gene and protein in 5 different EC cell lines with different pathological grades,Ishikawa,Hec-1-A,Hec-1-B,RL95-2 and AN3 Ca.Evaluate the changes in the biological behaviors of tumor cells by knocking down or overexpressing FKBP38.1.Examine the levels of FKBP38 gene and protein expression in 5 different human EC cell lines by Realtime quantitative PCR and Western blot assays;2.Infect the cell line by lentiviral vectors to achieve stable knockdown or overexpression of FKBP38,and examine the change of FKBP38 protein expression by Western blot;3.Use Ed U and plate cloning methods to examine the changes in cell proliferation of endometrial cancer cells after the knockdown or overexpression of FKBP38;4.Use Transwell chamber(with/without matrigel)method to evaluate the changes in cell migration and invasion ability of endometrial cancer cells after the knockdown or overexpression of FKBP38.Results:1.Low gene and protein expression levels of FKBP38 are inversely associated with high pathological grades in EC cells(based on the International Federation of Gynecology(International Federation of Gynecology and Obstetrics,FIGO);2.The knock down of FKBP38 expression in Ishikawa cells significantly increased cell proliferation ability,whereas overexpression of FKBP38 in AN3 Ca cells significantly reduced proliferation ability;3.The knock down FKBP38 expression in Ishikawa and RL95-2 cells significantly enhanced cell migration and invasion ability.The overexpression of FKBP38 in AN3 Ca and Ishikawa cells significantly reduced migration and invasion ability;4.The knock down of FKBP38 expression in Ishikawa cells significantly increased Phospho-S6 Ribosomal Protein(P-S6)levels,while overexpression of FKBP38 significantly decreased Phosphorylated protein kinase B(P-AKT)levels in AN3 Ca cells.Conclusion: The expression level of FKBP38 gene and protein is inversely related to the pathology grades of EC.Reduction of FKBP38 expression in EC cells can significantly promote proliferation,migration and invasion ability of the cancer cells.These biological effects of EC cells may be mediated by the activities of Ribosomal Protein S6(S6)or Protein kinase B(AKT)proteins.