title: Suppression of hepatitis B virus-derived human hepatocellular carcinoma by NF-kappaB-inducing kinase-specific siRNA using liver-targeting liposomes.
abstract: Hepatitis B virus triggers an increase of NF-kappaB inducing kinase (NIK)-dependent NF-kappaB activation, followed by the promotion of hepatocellular carcinoma (HCC). Here, we examined the inhibitory effect of NIK-specific siRNA on NF-kappaB 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 beta-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. beta-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.
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, 140-742, Korea.
authors.forename: Hyun-Ah
authors.initials: HA
authors.lastname: Cho
authors.forename: In-Sung
authors.initials: IS
authors.lastname: Park
authors.forename: Tae-Woo
authors.initials: TW
authors.lastname: Kim
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.forename: Ki-Sook
authors.initials: KS
authors.lastname: Yang
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Kim
mesh_terms: D037263:Asialoglycoprotein Receptor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy* / Q000821:virology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015316:Genetic Therapy / Q000379:methods*; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy* / Q000821:virology; D008190:Lyases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D012855:Sitosterols / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D037263:Asialoglycoprotein Receptor; D006514:Hepatitis B Surface Antigens; D008055:Lipids; D008081:Liposomes; D008190:Lyases; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012855:Sitosterols; D000097782:NF-kappaB-Inducing Kinase; C011015:lyoniside