| BackgroundOvarian cancer is one of the most common malignant tumors of female genital organs.Epithelial ovarian cancer accounts for 2/3 of ovarian cancer patients.When diagnosed,about 70%of epithelial ovarian cancer patients have developed into the advanced stage,with whose five year survival rate is less than 30%.So the diagnosis and treatment of epithelial ovarian cancer are challenging.By studying the molecular mechanisms of tumor growth,invasion and metastasis,it is helpful to find new effective therapeutic targets.A number of studies have shown that epithelial ovarian cancer is active in angiogenesis and that new blood vessels support for tumor growth,especially providing the necessary oxygen and nutrients to the tumor's internal tissues.At the same time,tumor cells can synthesize and secrete certain protein components by themselves,which can induce the surrounding normal host tissues to produce new blood vessels and fuse with tumor tissues.Vascular endothelial growth factor(VEGF)is the most important factor in promoting angiogenesis,and it can bind to VEGF receptor(VEGFR)to play a role in angiogenesis.IL-8 is a chemotactic cytokine that can be secreted by a variety of cells.It is highly expressed in varieties of malignancies and is closely related to the development and progression of tumors.However,the expression of IL-8 in ovarian cancer and its relationship with angiogenesis in cancer tissue still need further investigation.Our previous experimental results showed that the peripheral blood IL-8 concentration in patients with epithelial ovarian cancer increased,and the expression of VEGFR in epithelial ovarian cancer tissue increased significantly,and there was a significant positive correlation with the peripheral blood IL-8 concentration and VEGFR.On this basis,the ovarian cancer SKOV-3 cell line was further used as a model.In vitro,IL-8 could promote the expression of VEGFR in this cell line.It is helpful to understand the pathogenesis of ovarian cancer and provide a new target for immunotherapy.ObjectiveOur aim is to investigate the relationship between interleukin 8(IL-8),vascular endothelial growth factor receptor(VEGFR)and epithelial ovarian cancer,find the pathogenesis of ovarian cancer,find a target for gene diagnosis and treatment.Methods1.Detecte the IL-8 levels of healthy controls,epithelial ovarian cancer patients and benign ovarian tumors by ELISA.2.Analyze the vascular distribution characteristics in ovarian epithelial cancer by pathology,and detect the VEGFR expression in epithelial ovarian cancer tissue by immunohisto-chemical method.3.Analyze the correlation between serum IL-8 and VEGFR expression in cancer tissues of patients with epithelial ovarian cancer.4.Using RT-PCR to detect the expression of VEGFR mRNA in epithelial ovarian cancer cell lines SKOV-3 which stimulated by IL-8.5.Using immunofluorescence to detect the expression of VEGFR protein in epithelial ovarian cancer cell lines SKOV-3 which stimulated by IL-8.6.Statistical methods:measurement data were expressed as(?)± SD,the difference between the two groups using t test,multiple samples between mean compared by analysis of variance,correlation analysis using Person correlation test,the test level of alpha =0.05,P<0.05 difference was statistically significant.Results1.The concentration of IL-8 in peripheral blood serum of patients with epithelial ovarian cancer increased:the concentrations of IL-8 in peripheral blood serum were tested by ELISA,results showed that the concentration of IL-8 in peripheral blood serum of HC was(9.17 ± 2.07)pg/ml,patients with benign ovarian tumor was(10.70 ± 2.58)pg/ml.There was no significant difference between the two groups.The concentration of IL-8 in peripheral blood serum of patients with epithelial ovarian cancer was(24.50 ± 8.82)pg/ml,significantly higher than that of healthy controls and benign ovarian tumors,and there were statistical differences(P<0.0001;P<0.001).2.Angiogenesis were common in the tissue of patients with epithelial ovarian cancer,and the expression of VEGFR increased:pathological map showed that angiogenesis were common in the tissue of patients with epithelial ovarian cancer,and cancer cells showed epithelioid changes,nuclear polymorphism.Immuno-histochemistry showed that VEGFR was highly expressed in the tissues of patients with different epithelial ovarian cancer,except that it was expressed centrally in the vascular wall of new blood vessels,and also expressed in cancer cells.3.There was a positive correlation between the content of IL-8 in peripheral blood and the expression of VEGFR in tissue of patients with epithelial ovarian cancer:there was a positive correlation between the content of IL-8 in peripheral blood and the expression of VEGFR in tissue of patients with epithelial ovarian cancer(R=0.750),and there was statistical difference(P<0.0001).4.IL-8 stimulated the expression of VEGFR mRNA in epithelial ovarian cancer line SKOV-3 with a concentration dependent manner:in vitro,SKOV-3 was cultured with low concentration(1 pg/ml),middle concentration(4 pg/ml)and high concentration(16 pg/ml)of IL-8 fusion protein,and the expression of VEGFR mRNA was detected by RT-PCR after 16h,we found that the group without IL-8,the expression of VEGFR mRNA were(18.40 ± 6.55),while the expression of VEGFR mRNA were(30.70 ± 4.22),(50.10 ± 7.64)and(104.90 ± 9.21)in low,middle and high IL-8 groups,respectively.Compared with no IL-8 group,there were statistically significants(all P<0.05).In addition,these increases showed a concentration dependence(all P<0.05).5.IL-8 stimulated the expression of VEGFR protein in epithelial ovarian cancer line SKOV-3:the expression of VEGFR protein was detected by immunofluorescence combined with confocal laser.We found that the group without IL-8 stimulation hardly expressed VEGFR protein,when adding high concentration of IL-8,the cell line signif-icantly highly expressed VEGFR protein.ConclusionsIL-8 may promote the development of epithelial ovarian cancer by increasing the expression level of VEGFR. |
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