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Cancer Chemother. Pharmacol. · Oct 2005
Peroxisome proliferator activated receptor-gamma ligands induced cell growth inhibition and its influence on matrix metalloproteinase activity in human myeloid leukemia cells.
- Jiajun Liu, Huiling Lu, Renwei Huang, Dongjun Lin, Xiangyuan Wu, Qu Lin, Xinyao Wu, Jing Zheng, Xianglin Pan, Jun Peng, Yuqin Song, Maohong Zhang, Ming Hou, and Feng Chen.
- Department of Haematology and Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong Guangzhou, 510630, P.R. China, liujj@gzsums.edu.cn.
- Cancer Chemother. Pharmacol. 2005 Oct 1; 56 (4): 400-8.
AbstractPeroxisome proliferator-activated receptor-gamma (PPAR-gamma) is one of the best characterized nuclear hormone receptors (NHRs) in the superfamily of ligand-activated transcriptional factors. PPAR-gamma ligands have recently been demonstrated to affect proliferation, differentiation and apoptosis of different cell types. The present study was undertaken to investigate PPAR-gamma ligands induced cell growth inhibition and its influence on matrix metalloproteinase MMP-9 and MMP-2 activities on leukemia K562 and HL-60 cells in vitro. The results revealed that PPAR-gamma expression was detectable in the two kinds of leukemia cells; Both 15-deoxy-delta(12,14)-prostaglandin J2(15d-PGJ2) and troglitazone (TGZ) have significant growth inhibition effects on these two kinds of leukemia cells. These two PPAR-gamma ligands could inhibit the leukemic cell adhesion to the extracellular matrix (ECM) proteins and the invasion through matrigel matrix. The expressions of MMP-9 and MMP-2 as well as their gelatinolytic activities in both HL-60 and K562 cells were inhibited by 15d-PGJ2 and TGZ significantly. We therefore conclude that PPAR-gamma ligands 15d-PGJ2 and TGZ have significant growth inhibition effects on myeloid leukemia cells in vitro, and that PPAR-gamma ligands can inhibit K562 and HL-60 cell adhesion to and invasion through ECM as well as downregulate MMP-9 and MMP-2 expressions. The data suggest that PPAR-gamma ligands may serve as potential anti-leukemia reagents.
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