Targeting neurokinin-3 receptor: a novel anti-angiogenesis strategy for cancer treatment.
Targeting neurokinin-3 receptor: a novel anti-angiogenesis strategy for cancer treatment.
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靶向神经激肽3受体：癌症治疗的新型抗血管生成策略
DOI：
10.18632/oncotarget.17250
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发表时间：
2017-06-20
期刊：
影响因子：
--
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Wang T;Chen S;Wang S;Shi L;Wang C;Zhang J;Gao Y;Li G;Qi Y;An X;Chen L
血管生成是肿瘤生长和转移的必要条件，控制血管生成是肿瘤治疗的重要手段。然而，抗血管生成药物的严重副作用已被进一步证实，这激发了人们寻找抗血管生成新靶点的兴趣。神经激肽受体又称速激肽受体，由于其生理功能的多样性和易感性，通常被认为是药物靶点。虽然神经激肽B作为神经激肽-3受体的选择性天然激动剂已被证明具有抗血管生成活性，但神经激肽-3受体介导血管生成的作用和机制尚不清楚。在本研究中，我们证明了NKB的类似物[Mephe7]NKB对CAM具有显著的抗血管生成作用。此外，通过引入肿瘤血管生成归巢序列（NGR），我们设计并合成了NK3R的两种新型激动剂类似物，NK3R- a1和NK3R- a2。这两种类似物在体外通过激活NK3R对HUVECs表现出更有效的抗迁移作用，并且在体内显示出强大的抗肿瘤活性，无明显副作用。综上所述，我们的研究结果表明NK3R可能是抗血管生成治疗的潜在新靶点。值得注意的是，NK3R-A1可以作为基于抗血管生成策略的抗肿瘤药物开发的模板。
Angiogenesis is essential for tumor growth and metastasis, controlling angiogenesis is a promising strategy in cancer treatment. However, thus farther severe side effects of anti-angiogenic drugs have been rather demonstrated, stimulating interest in seeking novel targets of anti-angiogenesis. Neurokinin receptors, also known as tachykinin receptors, are usually considered as drug targets due to diverse physiological functions and their tractability. Although Neurokinin B, the selective natural agonist of neurokinin-3 receptor, have been shown to exhibit anti-angiogenesis activity, the effect and mechanism of neurokinin-3 receptor-mediated angiogenesis still remains unclear. In the present study, we demonstrated that [Mephe7]NKB, an analogue of NKB, possess significant anti-angiogenic effect on CAM. Furthermore, by introducing the tumor angiogenesis homing sequence (NGR), we designed and synthesized two novel agonist analogues of NK3R, NK3R-A1 and NK3R-A2. Both of the two analogues exhibit more efficient anti-migration effect on HUVECs by activating NK3R in vitro, and showed potent antitumor activities with no significant side effects in vivo. Taken together, our results illuminated that NK3R might be a potential novel target for the anti-angiogenesis therapy. Notably, NK3R-A1 might be used as a template for the development of the anti-tumor drugs on the basis of the anti-angiogenesis strategy.
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影响因子：
7.3
作者：
Hoveyda, Hamid R.;Fraser, Graeme L.;Blanc, Sebastien
通讯作者：
Blanc, Sebastien
DOI：
10.1038/nrc2442
发表时间：
2008-08
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.1
作者：
Al-Husein, Belal;Abdalla, Maha;Trepte, Morgan;DeRemer, David L.;Somanath, Payaningal R.
通讯作者：
Somanath, Payaningal R.
影响因子：
--
作者：
Ribatti D
通讯作者：
Ribatti D
影响因子：
82.9
作者：
Ellerby, HM;Arap, W;Pasqualini, R
通讯作者：
Pasqualini, R