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KMID : 0043320090320071077
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Archives of Pharmacal Research
2009 Volume.32 No. 7 p.1077 ~ p.1086
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Suppression of Hepatitis B Virus-derived Human Hepatocellular Carcinoma by NF-κB-inducing Kinase-specific siRNA using Liver- Targeting Liposomes
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Kim Jin-Seok
Yang Ki-Sook
Oh Yu-Kyoung
Kim Tae-Woo
Park In-Sung
Cho Hyun-Ah
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Abstract
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Hepatitis B virus triggers an increase of NF-κB inducing kinase (NIK)-dependent NF-κB activation, followed by the promotion of hepatocellular carcinoma (HCC). Here, we examined the inhibitory effect of NIK-specific siRNA on NF-κB signaling and HCC. The results of this study indicated that these siRNAs suppressed HBV-derived HCC by regulating NIK activation. To exert a protective effect from degradation enzyme, cationic liposomes were contrived and modified to contain β-sitosterol glucoside to target the asialoglycoprotein receptors in liver cancer cells. The cationic dimyristoyl diacyltrimethylammonium propane liposomes were prepared by a reverse-phase evaporation method with slight modification. β-Sitosterol glucoside was added to the lipid mixture at the beginning of the liposome preparation for the purpose of liver targeting. These liposomes assisted the delivery of the siRNA to specific cells and protected it from various lyases, followed by the ultimate suppression of HCC.
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KEYWORD
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siRNA, DMTAP, Beta-sitosterol glucoside, Liposomes, Hepatitis B Virus, NF-κB inducing kinase
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