Silencing of osteopontin promotes the radiosensitivity of breast cancer cells by reducing the expression of hypoxia inducible factor 1 and vascular endothelial growth factor / 中华医学杂志(英文版)
Chinese Medical Journal
;
(24): 293-299, 2012.
Article
in English
| WPRIM
| ID: wpr-333499
ABSTRACT
<p><b>BACKGROUND</b>Osteopontin (OPN) is a secreted phosphoglycoprotein (SSP) that is overexpressed in a variety of tumors and was regarded as a molecular marker of tumors. In this study, we intended to demonstrate the role of OPN in human breast cancer cell line MDA-MB-231.</p><p><b>METHODS</b>Recombinant plasmid expressing small interfering RNA (siRNA) specific to OPN mRNA was transfected into MDA-MB-231 cells to generate the stable transfected cell line MDA-MB-343, and the empty plasmid tansfected cells (MDA-MB-neg) or wildtype MDA-MB-231 cells were used as control cells respectively. Expression of OPN, hypoxia inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) proteins was analyzed by Western blotting analysis. The radiosensitivity of cells was determined by detecting cell apoptosis, cell proliferation and cell senescence.</p><p><b>RESULTS</b>HIF-1 and VEGF proteins in MDA-MB-343 cells were significantly downregulated upon the efficient knockdown of OPN expression under either hypoxia or normoxia environment. Moreover, expression of OPN protein was upregualted upon hypoxic culture. Stable OPN-silencing also decreased cell invasion, increased cell apoptosis and cell senescence, as well as reduced clonogenic survival, resulting in increase radiation tolerance.</p><p><b>CONCLUSIONS</b>Suppression of OPN gene expression can enhance radiosensitivity and affect cell apoptosis in breast cancer cells. OPN seems to be an attractive target for the improvement of radiotherapy.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Physiology
/
Radiation Tolerance
/
Breast Neoplasms
/
Gene Expression Regulation, Neoplastic
/
Reverse Transcriptase Polymerase Chain Reaction
/
RNA, Small Interfering
/
Cell Line, Tumor
/
Vascular Endothelial Growth Factor A
/
Hypoxia-Inducible Factor 1
/
Osteopontin
Limits:
Female
/
Humans
Language:
English
Journal:
Chinese Medical Journal
Year:
2012
Type:
Article
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