Oncotarget

Research Papers:

ATIQCTPC targeting MMP-9: a key step to slowing primary tumor growth and inhibiting metastasis of lewis lung carcinoma in vivo

Yuji Wang, Xinyi Xu, Ce Song, Jianhui Wu, Xi Hu, Haimei Zhu, Xiaoyi Zhang, Yaonan Wang, Lin Gui, Ming Zhao and Shiqi Peng _

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Oncotarget. 2017; 8:63881-63889. https://doi.org/10.18632/oncotarget.19172

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Abstract

Yuji Wang1, Xinyi Xu1, Ce Song3, Jianhui Wu1, Xi Hu1, Haimei Zhu1, Xiaoyi Zhang1, Yaonan Wang1, Lin Gui1, Ming Zhao1,2 and Shiqi Peng1

1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, China

2Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan

3Ruikang Hospital, Guangxi University of Chinese Medicine, Nanning, China

Corrospondence to:

Shiqi Peng, email: [email protected]

Ming Zhao, email: [email protected]

Ce Song, email: [email protected]

Keywords: MMP-9, tumor, metastasis, inflammation, TNF-α

Received: February 02, 2017   Accepted: June 02, 2017   Published: July 10, 2017

ABSTRACT

In this study we docked (6S)-3-acetyl-4-oxo-N-(2-(3,4,5,6-zetrahydroxytetrahydro-2H-pyran-2-carboxamido)ethyl)-4,6,7,12-tetrahydroindolo[2,3-a]quinolizine-6-carbo-xamide (ATIQCTPC) towards the active site of MMP-9, and showed that ATIQCTPC was able to effectively decrease the level of MMP-9 in the serum and the primary tumor of Lewis lung carcinoma (LLC) implanted C57BL/6 mice. As a MMP-9 inhibitor, ATIQCTPC inhibited the metastasis of LLC, and slowed the growth of the primary tumor of LLC implanted C57BL/6 in mice. The activities of ATIQCTPC to inhibit the ear edema and to decrease the serum levels of TNF-α and IL-8 of the mice treated with xylene were explored. The minimal effective dose of ATIQCTPC that can inhibit the primary tumour growth, prevent the metastasis of LLC and reduce the inflammatory response was 0.01 μmol/kg. The minimal effective dose of ATIQCTPC inhibiting tumour growth and metastasis was 100-fold lower than that of (S)-3-acetyl- 4-oxo-4,6,7,12-tetrahydroindolo[2,3-a]quinolizine-6-carboxylic acid (ATIQC, parent compound). The minimal effective dose of ATIQCTPC inhibiting inflammation was 110-fold lower than that of aspirin. These superiorities reflected the rationality of ATIQCTPC design. The safety of the therapy was explained by 1 μmol/kg of ATIQCTPC did not injure the kidney, the liver and the heart of the treated inflammation mice.


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