Simultaneous targeting therapy for lung metastasis and breast tumor by blocking the NF-κB signaling pathway using Celastrol-loaded micelles.
Simultaneous targeting therapy for lung metastasis and breast tumor by blocking the NF-κB signaling pathway using Celastrol-loaded micelles.
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使用雷公藤红胶束阻断 NF-κ B 信号通路同时靶向治疗肺转移和乳腺肿瘤
DOI：
10.1080/10717544.2018.1425778
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发表时间：
2018-11
期刊：
影响因子：
6
通讯作者：
Hu F
中科院分区：
文献类型：
--
作者：
Zhao Y;Tan Y;Meng T;Liu X;Zhu Y;Hong Y;Yang X;Yuan H;Huang X;Hu F
转移是乳腺肿瘤治疗成功的主要障碍之一。为了同时抑制乳腺肿瘤的转移和生长，建立了αvβ3配体四碘甲腺乙酸（泰特）修饰的南蛇藤酚（Cela）负载糖脂样缀合物（CSOSA/Cela）（TET-CSOSA/Cela），以阻断核因子-kappa B（NF-κB）信号通路。TET-CSOSA通过αvβ3受体介导的相互作用，在4 T1荷瘤小鼠肺转移瘤和原发瘤中的分布明显增加。结果表明TET-CSOSA/Cela通过阻断NF-κB，显著抑制肺转移瘤细胞Bcl-2的活化和4 T1乳腺癌细胞MMP-9的表达。TET-CSOSA/Cela对肺转移瘤和原发瘤的抑制率分别为90.72%和81.15%，而雷公藤红素的抑制率分别为72.15%和46.40%。结果表明，以αvβ3受体为靶点的TET-CSOSA/Cela胶束通过阻断NF-κB信号通路，具有同时治疗肺转移瘤和原发性肿瘤的潜力。
Metastasis is one of the major obstacles for successful therapy of breast tumor. To inhibit the metastasis and growth of breast tumor simultaneously, a Celastrol (Cela) loaded glucolipid-like conjugates (CSOSA/Cela) with αvβ3-ligand Tetraiodothyroacetic acid (TET) modification (TET-CSOSA/Cela) were established to block nuclear factor-kappa B (NF-κB) signaling pathway. The distribution of TET-CSOSA was remarkably increased in lung metastasis and primary tumor of 4T1 tumor-bearing mice by means of αvβ3 receptor-mediated interaction. The results demonstrated that TET-CSOSA/Cela significantly suppressed Bcl-2 activation of lung metastatic cells and reduced MMP-9 expression of 4T1 breast tumor cells by blocking NF-κB. The inhibitory rates of TET-CSOSA/Cela against lung metastasis and primary tumor were raised to 90.72 and 81.15%, compared to those of Celastrol (72.15 and 46.40%), respectively. All results demonstrated the αvβ3 receptor targeted TET-CSOSA/Cela micelles exhibited great potential in treating lung metastasis and primary tumor simultaneously via blocking NF-κB signaling pathway.
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