Depletion of OLFM4 gene inhibits cell growth and increases sensitization to hydrogen peroxide and tumor necrosis factor-alpha induced-apoptosis in gastric cancer cells

Journal of Biomedical Science

Research

Yi Huang¹  Li-ming Bao²  Rui-hua Liu³  Li-ya Wu⁴  Xue Jiang⁴  Na Ang⁴  Li-wen Yue⁵  Mei-hua Yang⁶  Hua-an Yang⁷  Hua Xiang⁸ 

[1] Center for Clinical Molecular Medicine; Ministry of Education Key Laboratory of Child Development and Disorders; Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders; Children's Hospital, Chongqing Medical University, 400014, Chongqing, China;Center for Clinical Molecular Medicine; Ministry of Education Key Laboratory of Child Development and Disorders; Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders; Children's Hospital, Chongqing Medical University, 400014, Chongqing, China;Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 45229, Cincinnati, USA;Center for Clinical Molecular Medicine; Ministry of Education Key Laboratory of Child Development and Disorders; Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders; Children's Hospital, Chongqing Medical University, 400014, Chongqing, China;Ministry of Education Key Laboratory of Laboratory Medical Diagnosis, Chongqing Medical University, 400016, Chongqing, China;Department of Biochemistry and Molecular Biology, Chongqing Medical University, 400037, Chongqing, China;Department of Health Care, Nanjing Maternity and Child Health Care Hospital, 210004, Nanjing, China;Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, 400037, Chongqing, China;Department of Urologic Surgery, Yubei Pepole's Hospital, 401120, Chongqing, China;Ministry of Education Key Laboratory of Laboratory Medical Diagnosis, Chongqing Medical University, 400016, Chongqing, China;

关键词: Gastric cancer;    Olfactomedin 4;    RNA interference;    Cell growth;    Apoptosis resistance;   

DOI  :  10.1186/1423-0127-19-38

 received in 2011-12-03, accepted in 2012-04-03,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundHuman 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.MethodsOLFM4 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.ResultsThe 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).ConclusionOur 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.

【 授权许可】

Unknown   
© Liu et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.