title: Suppression of HER-2 via siRNA interference promotes apoptosis and decreases             metastatic potential of SKOV‑3 human ovarian carcinoma cells.
abstract: The aberrant expression of human epidermal growth factor receptor-2 (HER-2)             has been detected in ovarian cancer. However, the role of HER-2 in the development             of ovarian cancer has not been sufficiently elucidated. The objective of this             study was to determine the role of HER-2 in the apoptosis and metastasis of SKOV-3             ovarian cancer cells. SKOV-3 cells were transfected with three double‑stranded             small interfering RNA (siRNA) molecules that target HER-2. Various sequences were             synthesized by T7 transcription in vitro to select the most effective HER-2‑silencing             siRNA. SKOV-3 cells were examined for growth inhibition using the MTT proliferation             assay and apoptosis was assessed using flow cytometry and TUNEL assay. The Matrigel             basement memebrane matrix was used to assess invasion and chemotactic mobility,             as a model of tumor cell metastasis. Western blot analysis was used to detect             the expression of matrix metallopeptidase-9 (MMP-9), E-cadherin, N-cadherin and             vimentin. siRNA interference in HER-2 resulted in decreased cell proliferation             and invasion and increased apoptosis. Western blot analysis demonstrated a marked             increase in E-cadherin and MMP-9 and a reduction in N-cadherin and vimentin protein             levels in the SKOV-3 cells. The suppression of HER-2 expression resulted in apoptosis             and the inhibition of metastasis of SKOV-3 cells. Therefore, the overexpression             of the HER-2 gene can enhance the metastatic potential of SKOV-3 cells by increasing             the protein levels of MMP-9. Epithelial-mesenchymal transition may be involved             in the HER-2 siRNA-induced invasion and migration of SKOV-3 cells. Taken together,             these results suggest that HER-2 functions as an oncogene and may thus be an attractive             therapeutic target in SKOV-3 ovarian cancer cells.
authors.affiliation: Department of Gynaecology and Obstetrics, The Affiliated Shengjing Hospital, China Medical University, Shenyang, PR China.
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Lu
authors.forename: Meng-Li
authors.initials: ML
authors.lastname: Rong
authors.forename: Chao
authors.initials: C
authors.lastname: Shang
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Zhao
authors.forename: Shu-Lan
authors.initials: SL
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human