ABSTRACT
OBJECTIVE@#To investigate effect and possible mechanisms of silencing human WFDC2 (HE4) gene on biological behavior changes as cell proliferation, apoptosis, movement and invasion of human serous ovarian cancer cell line SKOV3.@*METHODS@#Lentiviral WFDC2 gene sequence of small interfering siRNA was stablely transfected into SKOV3 identified by Q-PCR and western-blot. Obtained SKOV3 stable strains with silenced HE4 were measured by proliferation, apoptosis, migration, and invasion.@*RESULTS@#Gene sequencing showed that the oligonucleotides were successfully inserted into the expected site. After silencing HE4 in the SKOV3, proliferation was significantly inhibited (P<0.05). G(0)/G(1) phase was arrested by the cell cycle (P<0.01) and capacity of the migration and invasion decreased significantly (P<0.01). Slight early apoptosis ratio and no change of late apoptosis were found without change of Caspase-3 or Bcl-2 protein. Proteins involved in ERK pathway as phosphorylated protein as p-EGFR, p-ERK decreased and protease protein involved in tissue remodeling as matrix metalloproteinases MMP-9, MMP-2 and cathepsin B decreased compared with control group.@*CONCLUSIONS@#HE4 gene plays an important role in regulating proliferation, apoptosis, migration, invasion of serous ovarian cancer cells by ERK pathway and protease system. Its role in apoptosis needs to be further explored, and it may be a potential target for serous ovarian cancer.
Subject(s)
Female , Humans , Apoptosis , Genetics , Cell Cycle , Cell Line, Tumor , Cell Movement , Genetics , Cell Proliferation , Gene Knockdown Techniques , Gene Silencing , Physiology , Genetic Vectors , Lentivirus , Genetics , Neoplasm Invasiveness , Genetics , Ovarian Neoplasms , Genetics , Pathology , Proteins , Genetics , RNA, Small Interfering , Pharmacology , Transfection , WAP Four-Disulfide Core Domain Protein 2ABSTRACT
OBJECTIVE@#To investigate the value of serum human epididymis protein 4 (HE4) in differential diagnosis of patients with low-grade serous (LGSC) and high-grade serous carcinoma (HGSC) serous ovarian cancer.@*METHODS@#LGSC and HGSC serous ovarian cancer were diagnosed by the two-tier grade system, serum levels of HE4 and carbohydrate antigen 125 (CA125) were measured by ELISA and radioisotope method, respectively in 60 serous ovarian cancer patients. HE4 and TP53 protein in cancer tissue were measured by immunohistochemical method.@*RESULTS@#The difference in density of HE4 and TP53 protein was significant between LGSC and HGSC tissue, while serum CA125 did not show significant difference between different serum samples. There was significant difference in serum HE4 levels between LGSC and HGSC, and the result was different within FIGO (I+II) stage, suggesting HE4 was not a reliable biomarker for the discrimination between LGSC and HGSC. HE4 had potential as a biomarker for the discrimination between LGSC and HGSC but the role in early diagnosis was limited.@*CONCLUSIONS@#HE4 may be a reliable marker for differential diagnosis of LGSC and HGSC. But its role in early diagnosis of LGSC and HGSC need to be confirmed from the perspective of two-tier grade system.