Nuclear factor-kappa B inhibition can enhance therapeutic efficacy of 131I on the in vivo management of differentiated thyroid cancer

Aim: Nuclear factor-kappa B (NF-kappa B) plays a key role in cancer development and therapy resistance. We aimed to determine whether NF-kappa B inhibition can enhance I-131 efficacy in differentiated thyroid cancer (DTC) in vivo. Main methods: Every nude mouse was ip injected with 1 mCi of I-131 for thyroid ablation. Four weeks later. DTC cells were implanted. Another six weeks later, mice received four types of therapies, namely control vehicle, 1 mCi of I-131 once, 10 mg/kg of Bay 11-7082 (a NF-kappa B inhibitor) trice and combination treatment. Pre-ablation Tc-99m-pertechnetate imaging, post ablative and post therapeutic imaging were performed. Target-to-background ratios (T/Bs) on xenograft tumors were calculated and compared. Nuclear extract from tumor samples were assessed by DNA-binding assay and Western blot. Apoptotic indices by TUNEL assay were determined and tumor volume curve was drawn to compare therapeutic effects in different groups. Key findings: Post therapeutic imaging displayed I-131-avidity of xenograft tumors and completeness of thyroid ablation. T/Bs comparison showed no significant differences in mice received either I-131 mono-therapy or combined therapy. DNA-binding assay and Western blot showed enhanced function and expression of NF-kappa B by 1311, which were inhibited substantially by Bay 11-7082 combination. Apoptotic indices were significantly increased by combined treatment than by any mono-therapy. And DTC lesional volumes were significantly regressed by combined treatment than by any mono-therapy. Significance: We demonstrated that NF-kappa B inhibition can be a good interventional avenue to enhance therapeutic potentiation of I-131 on the in vivo management of DTC. (C) 2012 Elsevier Inc. All rights reserved.