| In vitro and in vivo study of cell growth inhibition of simvastatin on chronic myelogenous leukemia cells. | |
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MedLine Citation:
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PMID: 18824851 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Statins, a family of 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase inhibitors, are being investigated for the therapy and prevention of cancers. Here we aimed to investigate the effects of simvastatin on chronic myelogenous leukemia (CML) cells in vitro and in vivo, and to elucidate the mechanisms. METHODS: Cell proliferation and cell cycle were measured after K562 cells were incubated with simvastatin, and differentially expressed genes were determined by oligonucleotide microarray. Changes of 2 genes obtained by oligonucleotide microarray were validated by real-time RT-PCR, and immunohistochemistry was performed to determine expression of proliferating cell nuclear antigen (PCNA). Finally, a xenograft tumor model was constructed to evaluate the effects of simvastatin in vivo. RESULTS: Simvastatin could inhibit K562 cell proliferation, and the inhibition rate was approximately 30% after treatment with 20 mumol/l simvastatin for 48 h. Cell cycle was arrested in G(1) phase, as shown by flow cytometry results. Fifteen downregulated, 9 upregulated cell cycle-related genes and decreased PCNA protein were observed in the presence of simvastatin. Furthermore, simvastatin exhibited impairment of xenograft tumor growth in nude mice and also blocked cell cycle in G(1) phase. CONCLUSION: Simvastatin can inhibit CML cell proliferation in vitro and in vivo, and its mechanisms might be involved in cell cycle regulation. |
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Authors:
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Yong-Chang Yang; Wen-Fang Huang; Liang-Min Chuan; Dai-Wen Xiao; Ya-Li Zeng; Ding-An Zhou; Guo-Qiang Xu; Wen Liu; Bo Huang; Qi Hu |
Publication Detail:
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Type: Journal Article Date: 2008-09-30 |
Journal Detail:
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Title: Chemotherapy Volume: 54 ISSN: 1421-9794 ISO Abbreviation: Chemotherapy Publication Date: 2008 |
Date Detail:
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Created Date: 2008-10-21 Completed Date: 2008-12-16 Revised Date: 2009-11-11 |
Medline Journal Info:
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Nlm Unique ID: 0144731 Medline TA: Chemotherapy Country: Switzerland |
Other Details:
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Languages: eng Pagination: 438-46 Citation Subset: IM |
Copyright Information:
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2008 S. Karger AG, Basel. |
Affiliation:
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Clinical Laboratory Department, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Proliferation / drug effects Gene Expression Regulation, Neoplastic / drug effects Humans K562 Cells Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics, metabolism, pathology* Mice Mice, Nude Nuclear Proteins / genetics, metabolism Simvastatin / pharmacology* Xenograft Model Antitumor Assays |
| Chemical | |
Reg. No./Substance:
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0/Nuclear Proteins; 0/PCNP protein, human; 79902-63-9/Simvastatin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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