Increased Insulin-like Growth Factor 1 Activity Can Rescue KLE Endometrial-like Cells from Apoptosis

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Abstract
The peritoneal fluid (PF) of women with endometriosis contains protease(s) activity able to hydrolyze insulin-like growth factor-binding protein 3 (IGFBP-3), increasing the bioavailability of insulin-like growth factor-1 (IGF-1) locally. Therefore, we characterized the effects of IGF-1 on KLE endometrial-like cells in vitro. The mitogenic effect of IGF-1 was assessed by the analysis of the DNA content and cell count. Apoptosis was triggered experimentally by the 48 hr exposure of KLE cells to 100 nM of adriamycin in the presence and absence of IGF-1 (50 ng/ml). Adriamycin apoptosis of KLE cells was determined by the number of dead KLE cells using trypan blue exclusion and by the DNA fragmentation on simple agarose gel and flow cytometry of propidium iodide and HOECHST 33342-stained KLE cells using an EPICS 753 pulse cytometer. IGF-1 stimulated the growth of KLE cells in a dose-dependent manner (optimal dose of 50 ng/ml) and protected KLE cells from adriamycin (100 nM)-induced apoptosis. These data suggest that IGF-1 is a survival factor for KLE cells. Conceivably, increased IGF-1 activity in the PF can optimize both the survival and ectopic growth of endometrial cells in the peritoneal cavity.