Depletion of OLFM4 gene inhibits cell growth and increases sensitization to hydrogen peroxide and tumor necrosis factor-alpha induced-apoptosis in gastric cancer cells
| Autor: | Yi Huang, Liming Bao, Rui-hua Liu, Hua Xiang, Na Ang, Li-wen Yue, Li-ya Wu, Meihua Yang, Xue Jiang, Hua-an Yang |
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| Rok vydání: | 2012 |
| Předmět: |
Endocrinology
Diabetes and Metabolism Clinical Biochemistry Cell lcsh:Medicine Apoptosis Cysteine Proteinase Inhibitors Biology Amino Acid Chloromethyl Ketones Cell growth RNA interference Stomach Neoplasms Cell Line Tumor Granulocyte Colony-Stimulating Factor medicine Humans Pharmacology (medical) Molecular Biology Cell Proliferation Biochemistry medical Tumor Necrosis Factor-alpha Research lcsh:R Biochemistry (medical) G1 Phase Cancer Cell Cycle Checkpoints Hydrogen Peroxide Cell Biology General Medicine Cell cycle Oxidants medicine.disease Caspase Inhibitors Molecular biology Olfactomedin 4 medicine.anatomical_structure Cell culture Caspases Apoptosis resistance Cancer cell Tumor necrosis factor alpha Gastric cancer Gene Deletion |
| Zdroj: | Journal of Biomedical Science, Vol 19, Iss 1, p 38 (2012) Journal of Biomedical Science |
| ISSN: | 1423-0127 |
| DOI: | 10.1186/1423-0127-19-38 |
| Popis: | Background Human olfactomedin 4 (OLFM4) gene is a secreted glycoprotein more commonly known as the anti-apoptotic molecule GW112. OLFM4 is found to be frequently up-regulated in many types of human tumors including gastric cancer and it was believed to play significant role in the progression of gastric cancer. Although the function of OLFM4 has been indicated in many studies, recent evidence strongly suggests a cell or tissue type-dependent role of OLFM4 in cell growth and apoptosis. The aim of this study is to examine the role of gastric cancer-specific expression of OLFM4 in cell growth and apoptosis resistance. Methods 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 α) were assessed in the presence or absence of caspase inhibitor Z-VAD-fmk. Results 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 α-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 α-induced apoptosis in OLFM4 knockdown cells (all P < 0.01). Conclusion 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 α 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. |
| Databáze: | OpenAIRE |
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