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T. G. Papadaki, M. Tsilimbaris, I. Pallikaris, K. Thermos; Somatostatin Receptor (sst1- 5) Activation Leads to a Decrease in Proliferation of Human Retinal Pigment Epithelium (RPE) Cells in Culture. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2518.
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To investigate the differential effect of somatostatin (SRIF) and its receptor-specific analogues on the proliferation of human RPE cells in culture.
D407 cells were employed for all studies performed. MTT assay, APOpercentageTM apoptosis assay and trypan blue exclusion method were performed to study the cytostatic, apoptotic and necrotic effects of selective ligands of all somatostatin receptor subtypes (sst 1-5).
SRIF decreased cell proliferation in a concentration-dependent manner (1x10-10-1x10-4M). Similarly, activation of the five somatostatin receptor subtypes (sst1-5) mimicked the SRIF effect and decreased cell proliferation in a concentration-dependent manner. The decrease in cell number was due to cytostatic signaling (via sst 2, 3, 4 activation), apoptotic (via sst1 and sst5 activation) and cytotoxic effects at the highest concentration of ligands used (10-4M; mainly sst1 and sst5 activation). Sodium orthovanadate, a protein tyrosine phoshatases (PTPs) inhibitor, reversed the antiproliferative effects of SRIF.
This study provides novel information regarding the cytostatic, apoptotic and / or cytotoxic effects of SRIF in hRPE cells. These distinct signaling mechanisms are due to the differential activation of its receptors. Furthermore, the data suggest that SRIF influences RPE cell proliferation in a tyrosine-phosphatase dependent manner.
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