P0180 Effect of pioglitazone on proliferation and apoptosis in human uterine leiomyosarcoma cells

Abstract

Background SK-UT-1 cells, a human uterine leiomyosarcoma cell line, and human uterine smooth muscle cells (HutSMC) (controls) express the peroxisome proliferator-activated receptor γ (PPAR γ ). We investigated the effects of the PPAR γ agonist pioglitazone on the proliferation and induction of apoptosis in SK-UT-1 cells and HutSMC. Methods Cells were exposed to pioglitazone (10 or 25 μmol/l) in the presence or absence of the selective PPAR γ antagonist, GW 9226 (1 μmol/l). Cell proliferation was evaluated by WST-1 assay and cresyl violet staining. Western blot analysis was used to quantify the cleaved caspase-3, Bax, and Bad proteins. Cellular toxicity of pioglitazone was assessed by lactate dehydrogenase (LDH) release. Findings Pioglitazone increased the expression of the PPAR γ in SK-UT-1 cells and in HutSMC by a PPAR γ -dependent mechanism. Pioglitazone reduced cell proliferation in both quiescent and proliferating SK-UT-1 cells in concentration and time dependent fashion. These effects were partially mediated by PPAR γ . In SK-UT-1 cells, pioglitazone (25 μmol/l) activated caspase-3 and induced Bad, Bax, and p53 proteins. Higher levels of MEK and ERK and p-MEK and p-ERK were detected in quiescent SK-UT-1 cells than in quiescent HutSMC. Pioglitazone reduced p-ERK and p-MEK in SK-UT-1 cells in a time dependent manner, but did not alter p-MEK/MEK and p-ERK/ERK levels in HutSMC. Pioglitazone did not exert any cytotoxic effects in SK-UT-1 or HutSMC. Interpretation We demonstrate that pioglitazone reduces proliferation and promotes apoptosis in quiescent and proliferating leiomyosarcoma cells.