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


METHODS
Every nude mouse was ip injected with 1mCi of (131)I 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 (131)I once, 10mg/kg of Bay 11-7082 (a NF-κB inhibitor) trice and combination treatment. Pre-ablation (99m)Tc-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.


RESULTS
Post therapeutic imaging displayed (131)I-avidity of xenograft tumors and completeness of thyroid ablation. T/Bs comparison showed no significant differences in mice received either (131)I mono-therapy or combined therapy. DNA-binding assay and Western blot showed enhanced function and expression of NF-κB by (131)I, 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.


CONCLUSIONS
We demonstrated that NF-κB inhibition can be a good interventional avenue to enhance therapeutic potentiation of (131)I on the in vivo management of DTC.
Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, P.R. China. james_mencius@hotmail.com
Zhaowei
Z
Meng
Shanshan
S
Lou
Jian
J
Tan
Ke
K
Xu
Qiang
Q
Jia
Wei
W
Zheng
Shen
S
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D059248:Chemoradiotherapy / Q000379:methods*; D020287:In Situ Nick-End Labeling; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009570:Nitriles / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000532:radiotherapy*; D014183:Transplantation, Heterologous / Q000379:methods; D016896:Treatment Outcome
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D007457:Iodine Radioisotopes; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones