Targeting neurokinin-3 receptor: a novel anti-angiogenesis strategy for cancer treatment
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Ting Wang1,*, Siwei Chen1,*, Shihui Wang1, Liang Shi1, Chenggong Wang1, Jingxin Zhang1, Yanfeng Gao1, Guodong Li1, Yuanming Qi1, Xiuli An1 and Lixiang Chen1
1School of Life Science, Zhengzhou University, Zhengzhou, 450001, P.R. China
*These authors contributed equally to this work
Lixiang Chen, email: firstname.lastname@example.org
Yuanming Qi, email: email@example.com
Xiuli An, email: firstname.lastname@example.org
Keywords: anti-angiogenesis, neurokinin 3 receptor, neurokinin B, antitumor therapy
Received: August 16, 2016 Accepted: April 06, 2017 Published: April 19, 2017
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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