Enhancement of 131I therapeutic efficacy on differentiated thyroid cancer by nuclear factor-κB inhibitor in nude mice
10.3760/cma.j.issn.2095-2848.2013.02.008
- VernacularTitle:核因子-κB抑制剂增强131I治疗甲状腺癌疗效的裸鼠实验研究
- Author:
Zhaowei MENG
;
Qiang JIA
;
Shen WANG
;
Jian TAN
- Publication Type:Journal Article
- Keywords:
Thyroid neoplasms;
Cell apoptosis;
Iodine radiosotopes;
Mice,nude;
Nuclear factor-kappa B inhibitor;
Bay 11-7082
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2013;(2):129-133
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study whether Bay 11-7082,a nuclear factor-kappa B (NF-KB) inhibitor,could enhance the treatment efficacy of 131I on DTC in nude mice.Methods Total thyroid ablation nude mice models were prepared by intraperitoneal injection of 37 MBq 131I.The xenografted mice were divided into4 groups (18/group):131I group,Bay 11-7082 group,combination of 131I and Bay 11-7082 group and control group.Drug dosages were given as:intraperitoneal injection of 37 MBqT31I on day 1 in the 7th week in the 131I group; intraperitoneal injection of 10 mg/kg Bay 11-7082 on day 1,2 and 3 in the 7th week in the Bay 11-7082 group; intraperitoneal injection of both 131I and Bay 11-7082 as above-mentioned in the combined treatment group; injection of saline in the control group.The xenografted tumor volume curves were drawn every 7 days.Pertechnetate imaging was performed before thyroid ablation.Post-ablative and post-therapeutic 131I whole body imaging was conducted.On day 7 in the 7th week,6 mice in each group were sacrificed and apoptotic staining was performed on excised xenograft tumors.Apoptosis index was determined as positive cells over total ceils × 100％.One-way analysis of variance and q test were performed for statistical analysis.Results Thyroid and stomach could be visualized on pertechnetate imaging before thyroid ablation.Post-ablative 131I imaging showed increased uptake by the thyroid gland.Post-therapeutic 131I imaging showed increased uptake by the malignant tumor lesions in both the 131I and combined groups.Tumor volume curves showed significant differences in volume changes among different methods of therapy from the end of the 8th week (F =11.91-246.56,all P ＜ 0.01).Combined treatment was more effective than single-therapies (q =3.36-14.99,all P ＜ 0.01).Apoptosis indices for the control group,131I group,Bay 11-7082 group and combined group were (0.28 ±0.15)％,(5.49 ±0.69)％,(6.82 ±0.72)％ and (16.21 ± 1.57) ％,respectively (F =304.40,P ＜ 0.01).Apoptosis index in the combined group was significantly higher than those in each single therapy group (q =15.33 and 13.33,both P ＜ 0.01).Conclusion NF-κB inhibition by Bay 11-7082 could effectively enhance the treatment efficacy of 131I on DTC.
