Cho Hyun-Ah, Park In-Sung, Kim Tae-Woo, Oh Yu-Kyoung, Yang Ki-Sook, Kim Jin-Seok
College of Pharmacy, Sookmyung Women's University, Seoul, 140-742, Korea.
Arch Pharm Res. 2009 Jul;32(7):1077-86. doi: 10.1007/s12272-009-1714-z. Epub 2009 Jul 31.
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.
乙型肝炎病毒会引发核因子κB诱导激酶（NIK）依赖性核因子κB激活增加，进而促进肝细胞癌（HCC）的发生。在此，我们研究了NIK特异性小干扰RNA（siRNA）对核因子κB信号传导及肝细胞癌的抑制作用。本研究结果表明，这些siRNA通过调节NIK激活来抑制乙肝病毒衍生的肝细胞癌。为了免受降解酶的影响，制备并修饰了阳离子脂质体，使其含有β-谷甾醇葡萄糖苷，以靶向肝癌细胞中的去唾液酸糖蛋白受体。阳离子二肉豆蔻酰二酰基三甲基铵丙烷脂质体采用稍加修改的反相蒸发法制备。在脂质体制备开始时，将β-谷甾醇葡萄糖苷添加到脂质混合物中，以实现肝脏靶向。这些脂质体协助将siRNA递送至特定细胞，并保护其免受各种裂解酶的作用，最终抑制肝细胞癌。
