Suppression of hepatitis B virus-derived human hepatocellular carcinoma by NF-kappaB-inducing kinase-specific siRNA using liver-targeting liposomes.
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.
Cho
Hyun-Ah
HA
College of Pharmacy, Sookmyung Women's University, Seoul, 140-742, Korea.
Park
In-Sung
IS
Kim
Tae-Woo
TW
Oh
Yu-Kyoung
YK
Yang
Ki-Sook
KS
Kim
Jin-Seok
JS
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
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