Document Detail


Stable suppression of HER-2 gene expression using siRNA increases the lysis of human ovarian carcinoma cells mediated by NK-92 cell line.
MedLine Citation:
PMID:  19020724     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The overexpression and amplification of HER-2 gene is associated with the malignant biological behavior of ovarian carcinoma and these tumor cells expressing elevated levels of HER-2 appear to be resistant to the cytolysis of NK-92. In this study, we analyzed the cytolysis effects of NK-92 on human ovarian carcinoma cells (SK-OV-3) after inhibition the expression of HER-2 mRNA by siRNA. Human ovarian carcinoma cell line SK-OV-3 was transfected with siRNA-hairpin expression retroviral vector (HER-2/siRNA) designed to target HER-2 mRNA. A negative control was established utilizing a vector lacking the antisense component (HER-2/negative). The expression levels of HER-2 gene in SK-OV-3/siRNA, and SK-OV-3/negative cell lines were evaluated by semi-quantitative RT-PCR and immunohistochemistry. The growth and the early apoptosis of these cells were assayed by MTT and flow cytometry, respectively. The cytotoxicity of NK-92 against target cells was investigated by LDH. SK-OV-3/siRNA and SK-OV-3 cells were injected subcutaneously into BALB/c nude mice respectively and NK-92 cells were intraperitoneally injected to examine the anti-tumor activity in vivo. The stable cell line (SK-OV-3/siRNA) with a persistent silence of HER-2 was established. The inhibited expression of HER-2 gene was exhibited by semi-quantitative RT-PCR and immunohistochemistry. The suppressed proliferation and the elicitation of early apoptosis cells were observed in SK-OV-3/siRNA cell line. NK-92 cell line can efficiently lyse the SK-OV-3/siRNA cells in vitro and significantly inhibit the growth of tumors xenografted with SK-OV-3/siRNA cells. Suppression of HER-2 gene expression using siRNA combined treatment of NK-92 presents a new strategy for NK-92 biological treatment on the HER-2 expression epithelial tumors.
Authors:
Ying Zhou; Zhixiang Cheng; Huaiping Zhu; Dingqing Feng; Weidong Zhao; Bin Ling; Haiming Wei; Zhigang Tian
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncology reports     Volume:  20     ISSN:  1021-335X     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-21     Completed Date:  2009-02-04     Revised Date:  2010-09-03    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1425-31     Citation Subset:  IM    
Affiliation:
Anhui Province Key Laboratory of Molecular Medicine, Hefei 230001, P.R. China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Cell Line, Tumor
Female
Gene Expression Regulation, Neoplastic*
Genetic Vectors
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Transplantation
Ovarian Neoplasms / metabolism*
RNA, Small Interfering / metabolism*
Receptor, erbB-2 / metabolism*
Chemical
Reg. No./Substance:
0/RNA, Small Interfering; EC 2.7.10.1/ERBB2 protein, human; EC 2.7.10.1/Erbb2 protein, mouse; EC 2.7.10.1/Receptor, erbB-2

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