The Mechanism Of Estrogen To Increase The Metastasis Of Epithelial Ovarian Cancer Cells Via Regulation Of The Expression Of Hypoxia-inducible-factor-1α

I. Clinical ResearchObjectiveTo explore the relationship between the expression of HIF-1α, OPN, Cath-D and the prognosis and biological behaviour of epithelial ovarian cancer.MethodsImmunohistochemical staining is used in measuring the expressions of HIF-1α, OPN and Cath-D in paraffin-embedded specimen of ovarian clear cell adenocarcinoma, ovarian serous adenocarcinoma, and ovarian borderline and benign serous cystadenoma.ResultsThe expressions of HIF-1α, OPN and Cath-D are significantly higher in the malignant ovarian tumors than in the borderline or benign ones, which also correlated with staging, grade, lymph node metastasis and survival rates.ConclusionHigh or positively HIF-1α, OPN and Cath-D expression indicate unfavourable prognosis in ovarian cancer.Ⅱ. Foudation researchPart1The regulatory effect of estrogen on metastasis in ovarian clear cell and serous adenocarcinomaObjectiveTo investigate the effect of estrogen on metastasis of ovarian clear cell and serous adenocarcinoma and on the expression of the metastasis related cytokines OPN and Cath-D. MethodsTranswell chambers were used in the evaluation of the invasion ability of cancer cells. Change of protein levels of OPN and Cath-D after treated with estrogen was detected by Western Blotting.Results1. The invasion ability of SKOV3and ES-2cells treated with17β-estradiol was significantly elevated.2.17β-estradiol increased the expression of OPN and Cath-D in SKOV3and ES-2cells.ConclusionEstrogen upregulated the expression of OPN and Cath-D in SKOV3and ES-2cells, which promoted metastasis and invasion of the tumor cells.Part2The regulation of estrogen on expression of HIF-1α in the metastasis of ovarian cancerObjectiveTo explore the impact of estrogen on HIF-1α in ovarian clear cell and serous adenocarcinoma, and the relationship between HIF-1α and the expression of OPN and Cath-D.MethodsChange of HIF-1α protein level of SKOV3and ES-2cells after treated with estrogen was detected by Western Blotting. The cells were treated with sirolimus, an inhibitor of HIF-1α, or HIF-1α overexpression vector, and the expressions of OPN and Cath-D after treated with estrogen were detected by Western Blotting.Results17β-estradiol increased the expression of HIF-1α in SKOV3and ES-2cells. When HIF-1α was overexpressed, estrogen’s upregulation on OPN and Cath-D was reinforced. When HIF-1α was suppressed, estrogen’s upregulation on OPN and Cath-D was repressed. ConclusionThe effect of estrogen on metastasis in ovarian clear cell and serous adenocarcinoma was regulating by expression of HIF-1α and its targeting genes. OPN and Cath-D are the potential targeting genes of HIF-1α.Summary1. High or positively HIF-1α, OPN and Cath-D expression indicate unfavourable prognosis in ovarian cancer.2.17β-estradiol increased the expression of HIF-1α in SKOV3and ES-2cells. The effect of estrogen on metastasis in ovarian clear cell and serous adenocarcinoma was regulating by expression of HIF-1α and its targeting genes. OPN and Cath-D are the potential targeting genes of HIF-1α.