METHODS: RPE-19 cells were divided into three group: control group, hypoxia group(the final concentration of CoCl2 in the medium was 125 μmol/L), and Sim treatment group(3 μmol/L Sim was added in the RPE cells' medium which contain 125 μmol/L CoCl2). After 24h, the morphology of RPE-19 cells were observed, the proliferation of cells were calculated by MTT, the secretion levels and protein expression of hypoxia-inducible factor 1-Alpha(HIF-1α)and vascular endothelial growth factor(VEGF)were detected by enzyme-linked immunosorbent assay(ELISA)and Western blotting. The expression level of autophagy protein was detected by Western blot and apoptosis was detected by TUNEL.

RESULTS: The morphology and activity of RPE-19 cells showed an apparent change under hypoxia. The expression of HIF-1α and VEGF protein were increased obviously in the hypoxia group and then significantly decreased after Sim treatment. Beclin1, and LC3B proteins were decreased in the CoCl2+Sim group, and the expression levels were lower than the control and CoCl2 group. Under hypoxia, Sim inhibited RPE cells' proliferation and promoted the apoptosis.

CONCLUSION:Sim inhibits RPE cells' proliferation, decreases HIF-1α and VEGF protein, and promotes apoptosis under hypoxia. Our results suggested that the mechanism by which Sim promoted apoptosis in RPE cells may be related to its inhibition of autophagy.