| Epithelial ovarian cancer is one of the most frequent malignant tumors of female reproductive system, and the main reason of high mortality is that most of the patients found to be late or following widespread peritoneal metastasis. For patient with epithelial ovarian cancer, distant metastases are the major cause of mortality. Metastasis of the cancer is a interaction influence multi-step process. The most important step of metastasis is detachment of malignant cells from the primary tumor and invasion into surrounding tissue. In normal tissues, to limit cell free moving, cells are adhered by tight junction, gap junction and desmosome. However, the junctions of cancer cells are changed in order to make cells drop from primary tumor. The latest research indicates that epithelial-mesenchymal transition(EMT) plays an important role in tumor invasion and metastasis. EMT involves a series of changes through which epithelial cells lose their epithelial characteristics and acquire properties typical of mesenchymal cells. EMT facilitates cell movement and the generation of new tissue types during development and also contributes to the pathogenesis of disease. EMT is not only changed the phenotypic characteristics of epithelial cells, but also changed the molecular markers of tumor cells. The most typical characteristic change is epithelial marker calcium adhesion proteins(E-cadherin, E-cad) expression of decline or missing. E-cadherin is a 120 kD transmembrane glycoprotein coded by the E-cadherin gene located in chromosome 16q22.1. E-cadherin is a major of intercellular adhesion molecule, its function is mainly to maintain adhesion between epithelial cells and suppresses the freedom of the cells. Reducing E-cadherin expression leads the reducing of cell adhesion ability and enhancement cell movement ability. In recent years, many researchs have showed that E-cadherin low expression has correlation with tumor development in ovaian, gastric, hepatocellular, breast, bladder, esophageal, lung, and thyroid cancer. Therefore, E-cadherin is regarded as the tumor metastasis suppressor.Insulin like growth factor-I(IGF-I) is a 70 amino acid peptide in a single chain with three disulfide bonds and classified into four domains. IGF-1 is a polypeptide with amolecular weight of 7,649 kDa playing a key role in the regulation of cellular growth and metabolism. Studies have shown that IGF-1 in the serum of ovarian cancer patients with high expression increased risk of ovarian cancer, and promoted the development of epithelial ovarian cancer and reduced the prognosis of epithelial ovarian cancer. Some studies found IGF-1 induced cells epithelial-mesenchymal transformation by different signaling pathways in breast, prostate, gastric cancer and other tumors. But the role of IGF-1 in epithelial ovarian cancer has not been studied. Therefore, it is crucial to study the role of IGF-1 and epithelial-mesenchymal transition in the development of epithelial ovarian cancer.ObjectiveImmunohistochemical staining was conducted to detect the expression of IGF-1 and E-cadherin in the following tissue samples: 30 patients with epithelial ovarian cancer, 10 patients with borderline tumor, 10 patients with benign epithelial and 10 patients with normal ovaries. The expression changes of E-cadherin were observed by real-time reverse transcription-polymerase chain reaction(qRT-PCR) and Western blot after SKOV3 cells were treated with different concentrations IGF-1. The changes of invasion were detected by Transwell assay after SKOV3 cells were treated with different concentrations IGF-1.Methods1. Immunohistochemical staining was conducted to detect the expression of IGF-1 and E-cadherin in the following tissue samples: 30 patients with epithelial ovarian cancer, 10 patients with borderline tumor, 10 patients with benign epithelial and 10 patients with normal ovaries. To detect the relative of IGF-1 and E-cadherin in epithelial ovarian cancer tissues.2. The expression changes of E-cadherin were observed by real-time reverse transcription-polymerase chain reaction(RT-PCR) and Western blot after SKOV3 cells were treated with different concentrations IGF-1(0, 25, 50, 100,200 ng/ml).3. The changes of invasion were detected by Transwell assay after SKOV3 cells were treated with different concentrations IGF-1(0, 25, 50, 100, 200 ng/ml).Results1. The positive expression rate of IGF-1 in the group of epithelial ovarian cancer, borderline, benign and normal group were 73.3%, 30%, 20% and 10%. The expression of IGF-1 in the group of epithelial ovarian cancer was higher than the expression in the others and there was significant difference(H =17.647, P<0.050). There was no significant difference among other three groups(H =1.208, P>0.050).2. The positive expression rate of E-cadherin in the group of epithelial ovarian cancer, borderline, benign and normal group were 36.7%, 60%, 70% and 90%. The expression of E-cadherin in the group of epithelial ovarian cancer was lower than the expression in the others and there was significant difference(H =9.866,P<0.050). There was no significant difference among other three groups(H =1.208,P>0.050).3. The positive expression of IGF-1 and E-cadherin were related with the clinical stage, organization classification and two-tier grading syste(P<0.050), and no correlation with age and pathological type(P>0.050). In the epithelial ovarian cancer tissue IGF-1 and E-cadherin have negative correlation(r =-0.431,P<0.050).4. The expression of E-cadherin reduced after ovarian cancer SKOV3 cells were dealt with IGF-1.(P<0.050)5. IGF-1 promoted invasion of ovarian cancer SKOV3 cells after dealt with IGF-1 in a concentration-dependent manner.(P<0.050)Conclusions1. IGF-1 is a cancer-promoting factor, and E-cadherin is a tumor suppressor factor in epithelial ovarian cancer. In epithelial ovarian cancer tissues, IGF-1 and E-cadherin expression was negatively correlated.2. IGF-1 down-regulated E-cadherin in a dose-dependent manner, therefore, IGF-1 may be involved the EMT of epithelial ovarian cancer.3. IGF-1 enhanced invasion of ovarian cancer cells in a dose-dependent manner, therefore, IGF-1 may influence EMT by enhanced invasion of epithelial ovarian cancer. |
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