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In vitro and in vivo Study of Cell Growth Inhibition of Simvastatin on Chronic Myelogenous Leukemia Cells

Yang Y.-C.a · Huang W.-F.a · Chuan L.-M.a · Xiao D.-W.a · Zeng Y.-L.b · Zhou D.-A.b · Xu G.-Q.b · Liu W.b · Huang B.b · Hu Q.b
aClinical Laboratory Department, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, and bLaboratory Medicine Department, Chongqing Medical University, Chongqing, China Chemotherapy 2008;54:438–446 (DOI:10.1159/000158663)

Abstract

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 µmol/l simvastatin for 48 h. Cell cycle was arrested in G1 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 G1 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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