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)

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>