Nuclear factor-kappa B inhibition can enhance therapeutic efficacy of ¹³¹I on the in vivo management of differentiated thyroid cancer
2012
Meng, Zhaowei | Lou, Shanshan | Tan, Jian | Xu, Ke | Jia, Qiang | Zheng, Wei | Wang, Shen
AIM: Nuclear factor-kappa B (NF-κB) plays a key role in cancer development and therapy resistance. We aimed to determine whether NF-κB inhibition can enhance ¹³¹I efficacy in differentiated thyroid cancer (DTC) in vivo. MAIN METHODS: Every nude mouse was ip injected with 1mCi of ¹³¹I for thyroid ablation. Four weeks later, DTC cells were implanted. Another six weeks later, mice received four types of therapies, namely control vehicle, 1mCi of ¹³¹I once, 10mg/kg of Bay 11-7082 (a NF-κB inhibitor) trice and combination treatment. Pre-ablation ⁹⁹ᵐTc-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 ¹³¹I-avidity of xenograft tumors and completeness of thyroid ablation. T/Bs comparison showed no significant differences in mice received either ¹³¹I mono-therapy or combined therapy. DNA-binding assay and Western blot showed enhanced function and expression of NF-κB by ¹³¹I, 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-κB inhibition can be a good interventional avenue to enhance therapeutic potentiation of ¹³¹I on the in vivo management of DTC.
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