- 作者: Rui-hua Liu, Mei-hua Yang, Hua Xiang, Li-ming Bao, Hua-an Yang, Li-wen Yue, Xue Jiang, Na Ang, Li-ya Wu and Yi Huang
- 作者服務機構: 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, Chongqing, China
- 中文摘要: --
- 英文摘要:
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 alpha) 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 alpha-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 alpha-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 alpha 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.
- 中文關鍵字: --
- 英文關鍵字: Gastric cancer, Olfactomedin 4, RNA interference, Cell growth, Apoptosis resistance