Anti-inflammatory Effect of Pitavastatin on NF-κB Activated by TNF-α in Hepatocellular Carcinoma Cells(Molecular and Cell Biology)
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概要
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As nuclear factor-kappa B (NF-κB) is essential for promoting inflammation-associated cancer, it is a potential target for cancer prevention in chronic inflammatory diseases. Here we examined the anti-inflammatory effect of pitavastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on NF-κB activated by TNF-α in hepatocellular carcinoma (HCC) cells. Western blot revealed that the treatment of Huh 7 cells with pitavastatin at 0.1μM inhibited the nuclear expression of NF-κB p65 induced by TNF-α. Furthermore, electrophoretic mobility shift assay showed that after the cells were incubated with pitavastatin alone or with pitavastatin and TNF-α for 24h, pitavastatin significantly decreased the DNA binding activity of NF-κB induced by TNF-α. Subsequently, luciferase assay revealed that pitavastatin suppressed the transcriptional activity of the NF-κB promoter, which was clearly related to the HMG-CoA reductase activity because the addition of mevalonic acid (MEV) elevated the TNF-α activity. Moreover, the Rho kinase inhibitor Y27632 had no major effect on the NF-κB inhibitory activity of pitavastatin. The inhibitory effect of pitavastatin is possibly independent of the Rho kinase pathway in inflammation-associated HCC cells is. Finally, the addition of TNF-α significantly increased IL-6 protein production, which was suppressed by the addition of pitavastatin. These results suggest that pitavastatin at a low dose (0.1μM) inhibits NF-κB activation and decreases IL-6 production induced by TNF-α, and is therefore expected to be a new strategy for treating HCC.
- 公益社団法人日本薬学会の論文
- 2006-04-01
著者
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KITAJIMA Isao
Department of Laboratory Medicine, Kagoshima University School of Medicine
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Kitajima I
Department Of Clinical Laboratory Medicine Faculty Of Medicine Toyama University; 21st Century Coe P
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Kitajima Isao
Department Of Clinical And Laboratory Medicine Faculty Of Medicine Toyama Medical And Pharmaceutical
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TOKORO Takashi
Department of Ophthalmology of Tokyo Medical and Dental University
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Wang Juyong
Department of Orthopedics and Spinal Surgery, Graduate School, Tokyo Medical and Dental University
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Tokoro Takashi
Department Of Clinical Laboratory Medicine Faculty Of Medicine Toyama University; 21st Century Coe P
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Wang Juyong
Department Of Clinical Laboratory Medicine Faculty Of Medicine Toyama University; 21st Century Coe P
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Kitajima Isao
Department Of Laboratory Medicine Faculty Of Medicine 21st Century Coe Program Toyama Medical And Ph
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HIGA Susumu
Department of Laboratory Medicine, Faculty of Medicine, 21st Century COE Program, Toyama Medical and
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Higa Susumu
Department Of Clinical Laboratory Medicine Faculty Of Medicine Toyama University; 21st Century Coe P
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Wang Juyoung
Department Of Laboratory Medicine Faculty Of Medicine 21st Century Coe Program Toyama Medical And Ph
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Tokoro Takashi
Department Of Laboratory Medicine Faculty Of Medicine 21st Century Coe Program Toyama Medical And Ph
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