Research Papers:

Targeting neurokinin-3 receptor: a novel anti-angiogenesis strategy for cancer treatment

Ting Wang, Siwei Chen, Shihui Wang, Liang Shi, Chenggong Wang, Jingxin Zhang, Yanfeng Gao, Guodong Li, Yuanming Qi, Xiuli An and Lixiang Chen _

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Oncotarget. 2017; 8:40713-40723. https://doi.org/10.18632/oncotarget.17250

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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

Correspondence to:

Lixiang Chen, email: [email protected]

Yuanming Qi, email: [email protected]

Xiuli An, email: [email protected]

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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