title: Biodistribution and improved anticancer effect of NIK-siRNA in combination with 5-FU for hepatocellular carcinoma.
abstract: Increase of NF-κB inducing kinase (NIK) is known to promote the proliferation of the hepatitis B virus-derived hepatocellular carcinoma (HCC) cells. Previously, we have reported that NIK-specific siRNA in cationic liposomes was shown to suppress the expression of NIK and the proliferation of HCC cells (Cho et al., 2009). More improved suppression of NIK, followed by the improved antiproliferative effect on Hep3B cells, was achieved when 5-FU was co-treated with siRNA. Furthermore, biodistribution study after intravenous injection of siRNA into Hep3B-bearing Balb/c nude mice revealed that siRNA was highly accumulated in liver, followed by tumor, lung, spleen, kidney and heart. When encapsulated in cationic liposomes, larger amount of siRNA was found in tumor owing to the protection of siRNA from enzymatic degradation and enhanced permeability by liposome, suggesting a possible therapeutic modality of siRNA in liver-targeting cationic liposomal formulation for the treatment of hepatitis B virus-derived HCC.
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, Korea.
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kang
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Cho
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy / Q000821:virology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D006509:Hepatitis B / Q000150:complications; D007275:Injections, Intravenous; D008081:Liposomes; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010539:Permeability; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil; D008081:Liposomes; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D000097782:NF-kappaB-Inducing Kinase