Send to

Choose Destination
Cell Physiol Biochem. 2017;44(4):1640-1650. doi: 10.1159/000485764. Epub 2017 Dec 6.

Celecoxib Down-Regulates the Hypoxia-Induced Expression of HIF-1α and VEGF Through the PI3K/AKT Pathway in Retinal Pigment Epithelial Cells.



The goal of this study was to detect the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human retinal pigmented epithelial (RPE) cells treated with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, under hypoxic and normoxic conditions and to explore the signaling mechanism involved in regulating the hypoxia-induced expression of HIF-1α and VEGF in RPE cells.


D407 cells were cultured in normoxic or hypoxic conditions, with or without celecoxib or a PI3K inhibitor (LY294002). The anti-proliferative effect of celecoxib was assessed using the MTT assay. RT-PCR, Western blotting and ELISA were performed to detect the levels of PI3K, phosphorylated AKT (p-AKT), HIF-1α, VEGF and COX-2.


Celecoxib inhibited the proliferation of RPE cells in a dose-dependent manner. Celecoxib suppressed the expression of VEGF at both the mRNA and protein levels and decreased HIF-1α protein expression. HIF-1α activation was regulated by the PI3K/AKT pathway. The celecoxib-induced down-regulation of HIF-1α and VEGF required the suppression of the hypoxia-induced PI3K/AKT pathway. However, the down-regulation of COX-2 did not occur in cells treated with celecoxib.


The antiangiogenic effects of celecoxib in RPE cells under hypoxic conditions resulted from the inhibition of HIF-1α and VEGF expression, which may be partly mediated by a COX-2-independent, PI3K/AKT-dependent pathway.


Cyclooxygenase-2 inhibitor; Human retinal pigmented epithelial cells; Hypoxia-inducible factor 1α; PI3K/AKT pathway; Vascular endothelial growth factor

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for S. Karger AG, Basel, Switzerland
Loading ...
Support Center