• Wei-Hsun Wang, I-Tsang Chiang, Yu-Chang Liu, Fei-Ting Hsu, Hong-Wen Chen, Chuan-Lin Chen, Yi-Jang Lee, Wuu-Jyh Lin, and Jeng-Jong Hwang.
• 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
• In Vivo. 2013 May 1; 27 (3): 339-50.

AbstractFew 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.

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