title: Simultaneous imaging of temporal changes of NF-κB activity and viable tumor cells in Huh7/NF-κB-tk-luc2/rfp tumor-bearing mice.
abstract: Few studies have reported that the effect of sorafenib on advanced human hepatocellular carcinoma (HCC) is taking place via the inhibition of NF-κB signal transduction. Here we constructed a human HCC Huh7 stable clone with NF-κB-responsive element to drive dual reporter genes, herpes simplex virus thymidine kinase (tk) and firefly luciferase (luc2), and co-transfected with a third red fluorescent protein (rfp) gene, renamed as Huh7/NF-κB-tk-luc2/rfp cells, and combined with bioluminescent imaging (BLI) and red fluorescent protein imaging (RFPI) to monitor the effect of sorafenib on NF-κB activation and tumor inhibition. The results show that sorafenib could suppress the NF-κB-DNA binding activity, and the expression of downstream effector proteins. Notably, the relative photon fluxes obtained from RFPI and BLI, which represent the viable tumor cells and cells with NF-κB activation, decreased after sorafenib treatment by 50 to 65%, and 87.5 to >90%, respectively, suggesting that NF-κB activation is suppressed in viable HCC cells by sorafenib. Simultaneous molecular imaging of the temporal change of NF-κB activity and of viable cells in the same Huh7/NF-κB-tk-luc2/rfp tumors of the animal may reflect the real status of NF-κB activity and the viable tumor cells at the time of imaging.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155 Sec. 2 Li-Nong St., Bei-tou, Taipei 112, Taiwan, R.O.C. jjhwang@ym.edu.tw
authors.forename: Wei-Hsun
authors.initials: WH
authors.lastname: Wang
authors.forename: I-Tsang
authors.initials: IT
authors.lastname: Chiang
authors.forename: Yu-Chang
authors.initials: YC
authors.lastname: Liu
authors.forename: Fei-Ting
authors.initials: FT
authors.lastname: Hsu
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Chen
authors.forename: Chuan-Lin
authors.initials: CL
authors.lastname: Chen
authors.forename: Yi-Jang
authors.initials: YJ
authors.lastname: Lee
authors.forename: Wuu-Jyh
authors.initials: WJ
authors.lastname: Lin
authors.forename: Jeng-Jong
authors.initials: JJ
authors.lastname: Hwang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D057054:Molecular Imaging / Q000379:methods; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000077157:Sorafenib; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib