Expression And Clinical Significance Of EMT- Related Factors In Human Ovarian Cancer Cell Line And Ovarian Cancer Tissues

Objective:Ovarian cancer is a common malignant tumor of a female reproductive system with a high clinical incidence, and its mortality rate places in the top of gynecological malignancies causing a serious threat to women’s health and lives. Epithelial-mesenchymal conversion (epithelial-mesenchymal transition, EMT) is a special kind of cell differentiation, which plays an important physiological role in the normal development of human embryonic tissue, but it will also induce a variety of pathological changes and has in recent years gradually attracted more attention of researchers. EMT plays a role in many stages of development of a various cancers such as gastrointestinal cancer, skin cancer, breast cancer, ovarian cancer, hepatocellular carcinoma, pancreatic cancer and lung adenocarcinoma, in particular, EMT can promote invasion and metastasis of tumor tissue. EMT occurs in the tumor microenvironment being regulated and controlled by hypoxia-inducible factor-1α (HIF-1α), transcription factor Snail, E-cadherin adhesion and other inflammatory factors which are also the important reasons for development and distant organs metastasis of tumor tissues. This study aimed to investigate the expression and clinical significance of HIF-1α, Snail and E-cadherin in human mucinous ovarian cancer cell line 3AO, serous ovarian cancer cell line SKOV3, human clear cell ovarian cancer cell line ES-2 and human undifferentiated ovarian cancer cells strains the TYK and ovarian cancer tissues.Methods:Boyden chamber model was used to detect the invasion of 3AO, SKOV3, ES-2 and TYK ovarian cancer cells; western-blot and RT-PCR method were applied to detect the expression of HIF-1α, Snail and E-cadherin in human ovarian cancer cell line 3AO, SKOV3, ES-2 and TYK; immunohistochemistry was also used to analyze the expression of HIF-1α, Snail and E-cadherin in ovarian cancer tissue; correlation with the three proteins was analyzed as well as their relationship among age, histological grade, FIGO stage, histological type, myometrial invasion, lymph node metastasis and other clinicopathological factors.The results:1. The cell invasion numbers of human serous ovarian cancer cell line SKOV3, human clear cell ovarian cancer ES-2 were (132.6±6.4) and (130.4±5.6) per high-power field respectively, which were significantly higher than those of human undifferentiated ovarian cancer cell line TYK (102.3 ± 4.7) and human mucinous ovarian cancer cell line 3AO (104.1± 5.2) (P<0.01) per high-power field.2. Gene expression levels of HIF-1α:SKOV3> ES-2> 3AO> TYK; gene expression levels of Snail:SKOV3= ES-2> 3AO TYK; gene expression levels of E-cadherin: TYK> 3AO> SKOV3= ES-2 (P<0.05);3. Expression levels of HIF-la protein:SKOV3> ES-2> 3AO> TYK; expression levels of Snail protein:ES-2> SKOV3> 3AO> TYK; expression levels of E-cadherin protein; TYK= 3AO> ES-2> SKOV3 (P<0.05);4. The positive expression of HIF-la in ovarian cancer was significantly associated with histological grading, histological type and lymph node metastasis (P<0.05); Snail expression was significantly associated with surgical pathological staging, histological type and lymph node metastasis (P<0.05); E-cadherin positive expression was significantly associated with histological type and lymph node metastasis (P O.01);5. Expression of Snail was positively correlated with HIF-la in ovarian cancer (r= 0.231, P= 0.021), while Snail was negatively correlated with E-cadherin expression (r =-0.225, P= 0.028).In conclusion:HIF-la meybe inhibit the expression of E-cadherin by upregulating the expression of Snail, playing an important role in ovarian cancer invasion and metastasis.