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Investigational New Drugs
Published in: Investigational New Drugs 6/2010

01-12-2010 | PRECLINICAL STUDIES

Antimetastatic activity of MONCPT in preclinical melanoma mice model

Authors: Xiao-Chun Yang, Chong-Xing Tu, Pei-Hua Luo, Hong Zhu, Di-Feng Zhu, Hong-Hai Wu, Xing-Lu Zhou, Wei Lu, Qiao-Jun He, Bo Yang

Published in: Investigational New Drugs | Issue 6/2010

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Summary

Previous study demonstrated that MONCPT, a topoisomerase I inhibitor, exhibited potent anti-proliferation and anti-angiogenesis activity in vitro and in vivo. In this study, we report the efficacy of MONCPT against the development of melanoma metastasis by an intravenous injection of green fluorescent protein-transfected mice melanoma carcinoma (B16F10-GFP) cells in C57BL/6 mice. MONCPT (2.0, 5.0 and 12.5 mg/kg/2 days) markedly decreased B16F10-GFP pulmonary metastases by 12.8%, 53.1% and 76.3%, respectively; whereas higher doses of MONCPT (31.0 mg/kg/2 days) significantly inhibited the tumor growth of B16F10 xenograft model. In the in vitro experiment, MONCPT suppressed the B16F10-GFP cell invasion and migration without affecting cell survival. Further studies demonstrated that MONCPT decreased the secretion of matrix metalloproteinase (MMP)-9 and VEGF, and reduced the protein expression of HIF-1α as well as the phosphorylation level of ERK in B16F10-GFP cells. These in vivo and in vitro results indicate that MONCPT possesses both the potent antimetastatic ability and the tumor growth-inhibition activity, and the dual function promises MONCPT as a potential therapeutic agent for tumor metastasis and tumor growth of melanoma carcinoma.
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Metadata
Title
Antimetastatic activity of MONCPT in preclinical melanoma mice model
Authors
Xiao-Chun Yang
Chong-Xing Tu
Pei-Hua Luo
Hong Zhu
Di-Feng Zhu
Hong-Hai Wu
Xing-Lu Zhou
Wei Lu
Qiao-Jun He
Bo Yang
Publication date
01-12-2010
Publisher
Springer US
Published in
Investigational New Drugs / Issue 6/2010
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-009-9323-8

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