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First published online October 10, 2008
Experimental Biology and Medicine 233:1537-1545 (2008)
doi: 10.3181/0805-RM-164
© 2008 by the Society for Experimental Biology and Medicine
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ORIGINAL RESEARCH ARTICLE

Osteopontin Prevents Curcumin-Induced Apoptosis and Promotes Survival Through Akt Activation via {alpha}vβ3 Integrins in Human Gastric Cancer Cells

Gang Song*,{dagger},1, Yanlin Ming*,1, Yubin Mao*,{dagger}, Shideng Bao* and Gaoliang Ouyang*,2

* Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005, China; and {dagger} Cancer Research Center, Medical College, Xiamen University, Xiamen 361005, China

To whom requests for reprints should be addressed at 2 Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005, China. E-mail: oygldz{at}yahoo.com.cn

Osteopontin (OPN) is a secreted, integrin-binding matrix phosphorylated glycoprotein that is overexpressed in many advanced cancers. However, the functional mechanisms by which OPN contributes to gastric cancer development are poorly understood. Here, we report that curcumin inhibited the growth of SGC7901 cell and induced apoptosis in a concentration- and time-dependent manner, while the acquired expression of OPN in SGC7901 cells dramatically promoted cell survival under serum depletion and prevented curcumin-induced apoptosis. Furthermore, PI3-K inhibitor LY294002 attenuated OPN-mediated Akt activation. Moreover, inhibiting the binding of OPN to {alpha}vβ3 integrins reduced activation of Akt. Taken together, these results demonstrate that the pro-survival and anti-apoptosis activities of OPN in gastric cancer cells are mediated in part through PI3-K/Akt pathway via {alpha}vβ3 integrins.

Key Words: osteopontin (OPN) • gastric cancer • curcumin • apoptosis • Akt






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