The Preliminary Functional Study In Proliferation And Metastasis And Clinical Correlation Of Wip1 In Serous Ovarian Cancer

ObjectivesThe study was to invest the function of wip1 in ovarian cancer cells. Another purpose is to test the expression of wipl in serous ovarian cancer tissues, and to analyze the relation between wipl and survival of patients with ovarian cancer.Methods1. Retrovirus-mediated small hairpin RNA (shRNA) was used to silence the expression of wipl in ovarian cancer cell lines (A2780, Hey, Hey A8), and cDNA was transfected into ovarian cancer cell lines (SKOV3 and Ovca433) with Lipofectamine. Colony formation assay and growth curve were used to test cell proliferation. Flow cytometry was used to test cell cycle. Transwell, scratch assay, immunofluorescence, and Western blotting were used to test cell migration and invasion.2. Immunostaining of wipl was done in TMA with ovarian cancer samples. SPSS was used to analyze the clinical significance of wipl.Results1. Knockdown or overexpression of wipl was validated by Western blot and realtime PCR. Knockdown of wipl decreased the rate of cell growth and the number of clone, and the cell cycle was arrested in G1.Cell migration and invasion were blocked in ovarian cancer cells after knockdown of wipl. The protein level of wipl was opposite to that of E-cadherin, while was consistant with that of N-cadherin、MMP9、vimentin、 VEGF and the transcription factors slug and snail.2. The expression of wipl was detected in high-grade serous ovarian cancer tissues and had a positive correlation with platinum susceptibility (p=0.036), but no correlation with age, stage, ascites. Compared with weak expression, strong expression of wip1 predicted poorer overall survival (p=0.000) and disease-free survival (p=0.015).ConclusionsWip1 may play a role in proliferation and metastasis of ovarian cancer cells, and associate with EMT. The expression of wipl predicts high grade serous ovarian cancer patients’outcome and relates with the sensitivity to platinum.