| Objectives: Aurora-A, a member of a new serine/threonine kinase family, is a centrosome-associated protein and has been implicated in regulating centrosome function, spindle assembly, and chromosome segregation. Overexpression of Aurora-A is common in various cancers, which is associated with tumor formation, development and poor prognosis. Angiogenesis is essential for tumor growth and metastasis, therefore, anti-angiogenic therapy becomes one of the focuses in the treatment of cancer. This study aimed at elucidating the relationship between expression of Aurora-A,VEGF and their clinical significance in human serous ovarian cancer, then further exploring the pro-angiogenesis effect of Aurora-A on ovarian cancer.Methods: Immunohistochemical staining was performed to evaluate the expression of Aurora-A and VEGF in tumor tissue samples from 57 serous ovarian cancer patients. The correlation between Aurora-A and VEGF, their relationship with clinicopathological parameters and their impact on outcome were further investigated. The recombinant plasmids overexpression of Aurora-A were constructed and infected into SKOV3 cells, meanwhile the empty vectors were infected into SKOV3 cells as the control groups, and the level of Aurora-A expression were validated by Western Blot. Using these cells, the influence of Aurora-A on the Aurora-A protein expression was measured by ELISA kit. The supernatant of SKOV3 cells in different groups was collected to prepare conditioned medium. After incubating with conditioned medium, MTT assay, wound scratch assay, transwell assay and tube formation assay were used to further investigate the effect of Aurora-A on the ability of proliferation, migration, invasion, and tube formation of HUVECs.Results: 1. Positive expression of Aurora-A and VEGF proteins were, respectively, detected in 32(56.1%) and 36(63.2%) of the 57 SOC patients, and the expression of Aurora-A was significantly coincident with VEGF(r=0.604, P<0.001).Coexpression of these two proteins was associated with advanced FIGO stage, more malignant ascites, larger residual tumor size, presence of metastasis and increased likelihood of recurrence. Kaplan-Meier survival analysis revealed that patients with positive coexpression had worse progression-free survival(PFS) and overall survival(OS) than those with negative coexpression(P<0.001, respectively). Moreover, Cox regression analysis demonstrated that coexpression of Aurora-A and VEGF remains an independent factor for both PFS(P=0.035) and OS(P=0.03). 2. The plasmids were successfully transfected into SKOV3 cells, and high protein expression of Aurora-A in the gene-infected group than control group(empty vector-infected group) was validated by Western Blot. 3. ELISA kit demonstrated that Aurora-A could up-regulate the expression of VEGF in SKOV3 cells. 4. MTT assay indicated that, compared with the control group, the proliferation ability of HUVECs was significantly increased when treated with conditioned medium from SKOV3 cells overexpressing Aurora-A gene. 5. Wound healing assay showed that, compared with the control group, the migration ability of HUVECs was significantly enhanced when treated with conditioned medium from SKOV3 cells overexpressing Aurora-A gene. 6. Transwell assay showed that, compared with the control group, the invasion ability of HUVECs was significantly enhanced when treated with conditioned medium from SKOV3 cells cells overexpressing Aurora-A gene. 7. Tube formation assay revealed that, compared with the control group, the tube formation ability of HUVECs was significantly enhanced when treated with conditioned medium from SKOV3 cells overexpressing Aurora-A gene.Conclusions: 1. A positive correlation between the expression of Aurora-A and VEGF in SOC samples was observed, and coexpression of Aurora-A and VEGF predicts aggressive biological behaviors and poor outcome in serous ovarian carcinoma. 2. Aurora-A could positive regulate the expression of VEGF in ovarian cancer SKOV3 cells.3. Aurora-A could promotes proliferation, migration, invasion, and tube formation in endothelial cells. |
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