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Inhibition of proliferation and transforming growth factor β3 protein expression by peroxisome proliferators-activated receptor γ ligands in human uterine leiomyoma cells
Ist Teil von
Chinese medical journal, 2008-01, Vol.121 (2), p.166-171
Erscheinungsjahr
2008
Quelle
EZB Free E-Journals
Beschreibungen/Notizen
Background Rosiglitazone is known as the most potent and specific peroxisome proliferators-activated receptor γ (PPAR-γ) ligand. It has potentially far-reaching effects on pathophysiological processes, from cancer to atherosclerosis and diabetes. However, it is not clear whether rosiglitazone affects the protein expression of transforming growth factor β3 (TGF-β3) and the cell proliferation in human uterine leiomyoma cells in vitro.
Methods Human uterine leiomyoma tissues were dissected and cultured. Cells were divided into 5 groups: one control group and other four groups with different concentrations of rosiglitazone (10^-7, 10^-8, 10^-9 and 10^-10 mol/L). Cells were cultured for 72 hours in serum-free Dulbecco's modified Eagle's medium. MTT reduction assay was used to detect the cell proliferation. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of PPAR-γ and TGF-β3. Immunofluorescence staining was used to detect the expressions of PPAR-γ and TGF-β3 proteins.
Results MTT reduction assay indicated that the treatment with rosiglitazone (from 10^-7 to 10^-9 mol/L) resulted in an inhibition of the cell growths after 72 hours (P〈0.01). RT-PCR analysis revealed that 10^-7 mol/L rosiglitazone significantly affected the gene expression at 72-hour: PPAR-γ mRNA expression was up-regulated and TGF-β3 mRNA was down-regulated and rosiglitazone at the concentration of 10-7 mol/L affected these most effectively (P〈0.01). Immunofluorescence staining demonstrated that treatment with 10^-7 mol/L rosiglitazone resulted in the significant changes of PPAR-γ and TGF-β3 protein expressions compared with the other treatment groups and the control group at 72-hour (P〈0.01). All the effects of rosiglitazone on uterine leiomyoma cells were dose- and time-dependent in vitro.
Conclusions The present study demonstrates that the PPAR-γ activator, rosiglitazone, inhibits the cell proliferation partly through the regulations of PPAR-γ and TGF-β3 expressions. The cross-talk between the signal pathways of PPAR-γ and TGF-β3 may be involved in the process.