Correlation Between HMGB1and Ovarian Cancer Diagnosis And Develpment

ObjectiveHigh-mobility group box1(HMGB1), a pro-inflammatory cytokine, plays an important role in various inflammatory diseases such as septicemia and arthritis. Recent research of the role of HMGB1as cytokine involved in tumorigenesis and metastasis has opened up a new field of research to study the role of HMGB1in tumors. This study was to evaluate the serum levels of HMGB1in human ovarian tumor and healthy control, identify different HMGB1level before and after surgery, and to explore the inhibitory effect of HMGB1gene silencing on the proliferation and invasion ability of the human ovarian cancers and to observe the role of HMGB1on angiogenesis of human umbilical vein endothelial cells in vitro. Methods1. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum level of HMGB1in105ovarian cancer patients,46ovarian benign disease patients and33healthy control. Then we studied the serum levels of HMGB1in three groups and identified different HMGB1levels before and after treatment.2. Lentivirus vector with HMGB1shRNA was constructed and infected the ovarian cancer cell line SKOV3and A2780. The downregulation of HMGB1expression was observed under fluorescence microscopy.3. HMGB1expression was detected by RT-PCR and Western blot.4. CCK8was used for observing SKOV3、A2780cells proliferation.5. SKOV3、A2780cells invasion and migration was evaluated by a transwell chamber model.6. Human umbilical vein-derived endothelial cells (HUVECs) were treated with different concentrations of human rHMGBl or rVEGF-C. Changes in cell proliferation in vitro was assessed by CCK8assay.7.HUVECs migration in vitro was assessed by a transwell chamber assay.8. HUVECs capillary-like tube formation in vitro was assessed by a Matrigel model.Results1. Serum level of HMGB1was elevated in the malignant patients compared to the benign and control groups. In the malignant group, after therapy, the serum level of HMGB1decreased apparently.2. Down-regulation of HMGB1expression resulted in the inhibition of ovarian cancer cell biological behaviour and metastasis.3. Human rHMGB1promoted HUVECs proliferation, migration, and tube formation in a dose-dependent manner in vitro. As a specific angiogenesis factor, rVEGF-C induced angiogenesis significantly.Conclusion1. The serum HMGB1level was elevated in ovarian cancer patients, the serum HMGB1level decreased after therapy. HMGB1is closely associated with clinicopathologic features of ovarian cancer.2. Knockdown of HMGB1expression can significantly inhibit ovarian cancer cell proliferation, migration and invasion. All of this indicating that HMGB1may be severed as therapeutic target for ovarian cancer in the future.3. HMGB1might contribute to tumor angiogenesis and angiogenic metastasis, and this might suggest a possible therapeutic role in cancer.