Osteopontin prevents curcumin-induced apoptosis and promotes survival through Akt activation via alpha v beta 3 integrins in human gastric cancer cells.
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(v)beta(3) 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(v)beta(3) integrins.
Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005, China.
Gang
G
Song
Yanlin
Y
Ming
Yubin
Y
Mao
Shideng
S
Bao
Gaoliang
G
Ouyang
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D002999:Clone Cells; D016895:Culture Media, Serum-Free; D003474:Curcumin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D002867:Chromones; D016895:Culture Media, Serum-Free; D003474:Curcumin; D004791:Enzyme Inhibitors; D039302:Integrin alphaVbeta3; D009025:Morpholines; D053495:Osteopontin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one