title: Inhibition of proliferation and transforming growth factor beta3 protein expression by peroxisome proliferators-activated receptor gamma ligands in human uterine leiomyoma cells.
abstract: BACKGROUND
  Rosiglitazone is known as the most potent and specific peroxisome proliferators-activated receptor gamma (PPAR-gamma) 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 beta3 (TGF-beta3) 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-gamma and TGF-beta3. Immunofluorescence staining was used to detect the expressions of PPAR-gamma and TGF-beta3 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-gamma mRNA expression was up-regulated and TGF-beta3 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-gamma and TGF-beta3 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-gamma activator, rosiglitazone, inhibits the cell proliferation partly through the regulations of PPAR-gamma and TGF-beta3 expressions. The cross-talk between the signal pathways of PPAR-gamma and TGF-beta3 may be involved in the process.
authors.affiliation: Department of Obstetric and Gynecology, Shandong University Shandong Provincial Hospital, Jinan, Shandong 250021, China.
authors.forename: Chun-hua
authors.initials: CH
authors.lastname: Zhang
authors.forename: Ze-qing
authors.initials: ZQ
authors.lastname: Wen
authors.forename: Jian-feng
authors.initials: JF
authors.lastname: Li
authors.forename: Chang-zhong
authors.initials: CZ
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.forename: Gui-wen
authors.initials: GW
authors.lastname: Yang
authors.forename: Shou-min
authors.initials: SM
authors.lastname: Lan
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Yao-jing
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Ying-ying
authors.initials: YY
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy* / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists* / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D053782:Transforming Growth Factor beta3 / Q000032:analysis / Q000235:genetics*; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D053782:Transforming Growth Factor beta3; D000077154:Rosiglitazone