%0 Journal Article
%T Depletion of OLFM4 gene inhibits cell growth and increases sensitization to hydrogen peroxide and tumor necrosis factor-alpha induced-apoptosis in gastric cancer cells
%A Rui-hua Liu
%A Mei-hua Yang
%A Hua Xiang
%A Li-ming Bao
%A Hua-an Yang
%A Li-wen Yue
%A Xue Jiang
%A Na Ang
%A Li-ya Wu
%A Yi Huang
%J Journal of Biomedical Science
%D 2012
%I BioMed Central
%R 10.1186/1423-0127-19-38
%X OLFM4 expression was eliminated by RNA interference in SGC-7901 and MKN45 cells. Cell proliferation, anchorage-independent growth, cell cycle and apoptosis were characterized in vitro. Tumorigenicity was analyzed in vivo. The apoptosis and caspase-3 activation in response to hydrogen peroxide (H2O2) or tumor necrosis factor-alpha (TNF ¦Á) were assessed in the presence or absence of caspase inhibitor Z-VAD-fmk.The elimination of OLFM4 protein by RNA interference in SGC-7901 and MKN45 cells significantly inhibits tumorigenicity both in vitro and in vivo by induction of cell G1 arrest (all P < 0.01). OLFM4 knockdown did not trigger obvious cell apoptosis but increased H2O2 or TNF ¦Á-induced apoptosis and caspase-3 activity (all P < 0.01). Treatment of Z-VAD-fmk attenuated caspase-3 activity and significantly reversed the H2O2 or TNF ¦Á-induced apoptosis in OLFM4 knockdown cells (all P < 0.01).Our study suggests that depletion of OLFM4 significantly inhibits tumorigenicity of the gastric cancer SGC-7901 and MKN45 cells. Blocking OLFM4 expression can sensitize gastric cancer cells to H2O2 or TNF ¦Á treatment by increasing caspase-3 dependent apoptosis. A combination strategy based on OLFM4 inhibition and anticancer drugs treatment may provide therapeutic potential in gastric cancer intervention.Human OLFM4 (olfactomedin 4, also known as hGC-1, GW112), originally termed human cloned from myeloid precursor cells after granulocyte colony-stimulating factor stimulation [1], is a secreted glycoprotein more commonly known as the anti-apoptotic molecule GW112 [2,3]. OLFM4 is normally expressed in bone marrow, prostate, small intestine, stomach, colon and pancreas [1,4]. Subsequently, increased OLFM4 levels were also found in the crypt epithelium of inflamed colonic mucosa of inflammatory bowel diseases [5] and in gastric biopsies infected with Helicobacter pylori [6,7]. More recently, up-regulated OLFM4 expression has been described in lung and breast [8], prostatic [3], gastric [3
%K Gastric cancer
%K Olfactomedin 4
%K RNA interference
%K Cell growth
%K Apoptosis resistance
%U http://www.jbiomedsci.com/content/19/1/38