Ting Wang, Siwei Chen, Shihui Wang, Liang Shi, Chenggong Wang, Jingxin Zhang, Yanfeng Gao, Guodong Li, Yuanming Qi, Xiuli An, Lixiang Chen
Oncotarget 2017 Jun 20Angiogenesis 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.
Ting Wang, Siwei Chen, Shihui Wang, Liang Shi, Chenggong Wang, Jingxin Zhang, Yanfeng Gao, Guodong Li, Yuanming Qi, Xiuli An, Lixiang Chen. Targeting neurokinin-3 receptor: a novel anti-angiogenesis strategy for cancer treatment. Oncotarget. 2017 Jun 20;8(25):40713-40723
PMID: 28489574
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