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Annals of Oncology Advance Access published online on January 10, 2005
Annals of Oncology, doi:10.1093/annonc/mdi077
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© 2005 European Society for Medical Oncology
Received August 24, 2004
Revised September 26, 2004
Accepted October 5, 2004

Original Article

Expression of survivin and bax/bcl-2 in peroxisome proliferator activated receptor-{gamma} ligands induces apoptosis on human myeloid leukemia cells in vitro

J. J. Liu 1, R. W. Huang 1*, D. J. Lin 1, J. Peng 2, X. Y. Wu 1, Q. Lin 1, X. L. Pan 2, Y. Q. Song 3, M. H. Zhang 2, M. Hou 2, and F. Chen 2

1 Department of Hematology and Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
2 Department of Hematology and Oncology, Qilu Hospital of Shandong University, Jinan, China
3 Department of Oncology, Health Science Center of Peiking University, Beijing, P.R. China

* To whom correspondence should be addressed.
R. W. Huang, E-mail: huangrw56{at}163.com


  Abstract

The present study was undertaken to investigate the mechanisms of peroxisome proliferator activated receptor-{gamma} (PPAR-{gamma}) ligand-induced apoptosis on human myeloid leukemia K562 and HL-60 cell lines. The results revealed that both 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) and troglitazone (TGZ) have significant anti-proliferation- and apoptosis-inducing effects on these two kinds of leukemia cells. Marked morphological changes of cell apoptosis including condensation of chromatin and nuclear fragmentation were observed clearly using Wright's and Hoechst 33258 staining. Reverse transcription-PCR and western blot analyses demonstrated that both survivin and bcl-2 expression were downregulated markedly, while bax expression was upregulated concurrently when apoptosis occurred. We therefore conclude that 15d-PGJ2 and TGZ have significant apoptosis effects on K562 and HL-60 cells in vitro, and that upregulation of bax as well as downregulation of survivin and bcl-2 expression may be the important apoptosis-inducing mechanisms. The results suggest that PPAR-{gamma} ligands may serve as potential therapeutic agents for both acute and chronic myeloid leukemia.

Keywords: apoptosis; bax; bcl-2; PPAR-{gamma}; survivin.
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