Effects of progesterone and anti-progestin (mifepristone) treatment on proliferation and apoptosis of the human ovarian cancer cell line, OVCAR-3

Abstract

The study examined the effects of various progesterone and mifepristone concentrations on the proliferation and apoptosis of the human ovarian cancer cell line, OVCAR-3. OVCAR-3 cells were incubated with progesterone and mifepristone at concentrations ranging from 10(-3) to 10(-9) M. Proliferation and apoptosis were studied by means of inverted optical microscopy, DAPI staining, and crystal violet assay. Immunoblotting was used to study the regulation of the apoptosis-related proteins, bcl-2, caspase-3 and PARP, after incubation with various reagents. OVCAR-3 cell density was increased by progesterone concentrations of 10(-5) M or less, and decreased by 10(-3) M progesterone. DAPI staining showed no apoptotic bodies. Mifepristone concentrations of 10(-3) and 10(-4) M reduced the OVCAR-3 cell density. Immunoblotting showed PARP cleavage in the presence of mifepristone 10(-4) M. Caspase-3 and bcl-2 expression was reduced by mifepristone 10(-4) and 10(-7) M. These results suggest that progesterone has a paradoxical effect on OVCAR-3 cell proliferation, stimulating it at low concentrations and inhibiting it at high concentrations, potentially through a caspase-independent non-apoptotic death pathway. Mifepristone seems to inhibit OVCAR-3 cell proliferation by down-regulating bcl-2 and up-regulating caspase-3 activity. These preliminary results suggest that progesterone and mifepristone have beneficial effects in ovarian cancer.