| Endometrial cancer ranks as one of the most common gynecologic malignancy in China,the etiology of endometrial cancer is not clearly understood.Epidemiological data show that Metabolic syndrome related diseases,such as obesity、hypertension、type 2 diabetes and Polycystic ovarian syndrome are widely accepted risk factors for EC.The metabolic syndrome is a cluster of risk factors that includes central adiposity,high blood pressure,elevated blood glucose levels,elevated triglycerides,and so on Metabolic syndrome may be an important etiologic factor for the development and progression of certain types of cancer and also for overall cancer mortality.As an important endocrine organ,adipose tissue secretes a number of bioactive peptides or proteins,collectively named“adipokines",such as adiponetcin,leptin,resistin,PAI-1 and TNF-α.They play a central role in obesity-related diseases as well as oncogenesis.Visfatin was identified as a brand new member of adipokines Accumulated evidences indicate that visfatin is correlated to various malignant tumors,especially Metabolic syndrome related cancers,such as breast cancer,colorectal cancer and gastric cancer.Visfatin may play as a molecular link between Metabolic syndrome and cancers.The correlation between visfatin and endometrial cancer has not been reported yet,In the current study,the role played by visfatin in the development of endometrial cancer will be discussed in three sectionsSection One The Association of visfatin and Endometrial Cancer RiskObjective:The aim of this study was to assess the clinical significance of serum levels and tissue expression of visfatin in relation to endometrial cancer(EC)Methods:A total of 234 EC patients were included in this study.Serum visfatin,metabolic and anthropometric parameters were measured in EC patients and controls Serum visfatin levels were detected using ELISA.Tissue expression of visfatin was analyzed using immunohistochemistry in tissue microarrays.The correlation between clinicopathological variables and visfatin in EC tissues and the prognostic value of visfatin for overall survival was evaluatedResults:Serum levels of visfatin were significantly higher in EC patients than in controls(P<0.05).In univariate and multivariate logistic regression models,a positive association between EC and serum visfatin,BMI,waist-to-hip ratio,diabetes,and hypertension was evident(P<0.05).Visfatin expression was significantly higher in EC tissue than in normal endometrial tissue(P=0.001).Moreover,serum visfatin levels were significantly positively correlated with tissue expression of visfatin in EC patients(P<0.05).High visfatin expression in EC tissues was significantly associated with advanced FIGO stage(P=0.016)and myometrial invasion≥1/2(P=0.023).The overall survival rate of EC patients was significantly higher in the group with negative visfatin expression than with positive visfatin expression(P=0.035).Conclusions:Visfatin is a potential serum biomarker and prognostic factor for EC that may indicate high risk for EC and EC progression.It may also be a novel potential therapeutic target for EC.Section Two The effect of visfatin on the biological behavior of endometrial cancer cell line Objective:To investigate the effect of human recombinant visfatin on the biological behavior of endometrial cancer cell lines in vitroMethods:Ishikawa and KLE cell lines were used in this current study.cell pliferation was analysed using the CCK-8 assay kit according to the manufacturer’s instructions.Flow cytometry for cell cycle analysis and cell apoptosis analysis.Transwell system was used to investigate the influnce of visfatin on cell migration and metastasisResults:Ishikawa and KLE cell viability determined by absorbance at OD 450 nm was increased by visfatin(P<0.05).The cell cycle analysis revealed that visfatin induced a significant decrease of G1,but an increased S phase of the cells within 24 h of serum-starvated conditions(P<0.05),The proportion of apoptotic cells was significantly decreased treated by visfatin(P<0.05).visfatin promoted migration and invasion of Ishikawa and KLE cell(P<0.05).Conclusions:Visfatin plays a central role on promoting endometrial cancer cell proliferation,G1/S cell cycle progression,apoptosis suppression and promoting migration and invasion in vitroSection Three PI3K/Akt and MAPK/ERK1/2 signalling pathways were involved in visfatin-induced Poor biological behavior of endometrial cancer cellObjective:To investigate the molecular mechanism involved in poor biological behavior induced by visfatin of endometrial cancer cell in vitroMethods:Western blotting to detect the expression of C-MYC,CyclinD1,MMP2 and Caspase 3,Akt,p-Akt,ERK1/2,p-ERK1/2,InsR,p-InsR,IRS1,p-IRS1,IRS2,p-IRS2 in Ishikawa and KLE cells with or without visfatin treatment.To examine the expression of C-MYC,CyclinD1,MMP2 and Caspase 3 and to investigate the effect of visfatin on the biological behavior of endometrial cancer cell lines again pretreated with LY294002,an inhibitor of PI3K or/and U0126,an inhibitor of MEKResults:Expression of C-MYC,CyclinD1,MMP2 were increased and Caspase 3 was decreased in Ishikawa and KLE cell treated by visfatin(P<0.05).Enhanced phosphorylation level of Akt,ERK1/2,InsR,IRS1,IRS2 were detected in time-dependent manner(P<0.05),Inhibition of PI3-kinase by the inhibitor LY293002 and Inhibition of ERK1/2 by the inhibitor U0126 abolished visfatin-induced increasement of C-MYC,CyclinD1,MMP2 and also abolished decreasement of Caspase 3(P<0.05).LY294002 or/and U0126 abolished the effect of cell proliferation,Gl/S cell cycle progression,apoptosis suppression and cell metastasis(P<0.05)Conclusions:PI3K/Akt and MAPK/ERK1/2 signalling pathways were involved in visfatin-induced Poor biological behavior of endometrial cancer cell... |
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