Investigational New Drugs

, Volume 28, Issue 6, pp 800–811 | Cite as

Antimetastatic activity of MONCPT in preclinical melanoma mice model

  • 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


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.


MONCPT Metastasis Melanoma Antitumor 





green fluorescent protein


matrix metalloproteinase


hypoxia induced factor


vascular endothelial growth factor


Mitogen-activated protein kinase



This study was financially supported by grants from National Natural Science Foundation of China 30801406, Zhejiang Provincial Foundation of Natural Science for Outstanding Youths (R2080326), Zhejiang Provincial Foundation of Natural Science (Y2080479), the Health Foundation of Zhejiang Province (2008A044), the Foundation of High-tech Talents of Cao Guangbiao, and Zhejiang Provincial Program for the Cultivation of Innovative Undergraduates.

Supplementary material

10637_2009_9323_Fig6_ESM.gif (151 kb)
Supp. 1

Histologic sections stained with H&E show lung metastatic lesions. (A) H&E staining of lungs of mice injected with B16F10-GFP (Black arrows: metastatic lesions; ×100). (B) H&E staining of lungs of normal C57BL/6 mice (×100). (152 KB)

10637_2009_9323_Fig6_ESM.tif (2.9 mb)
High Resolution Image (TIFF 2986 kb)
10637_2009_9323_Fig7_ESM.gif (5 kb)
Supp. 2

Effect of MONCPT on B16F10-GFP cells viability. 5 × 103 cells were seeded in 96 multiware. After 8 h attachment, replace with serum free medium and various dose of MONCPT were added. After 24 h, cell viability was determined by SRB assay. (8.00 KB)

10637_2009_9323_Fig7_ESM.tif (1.4 mb)
High Resolution Image (TIFF 1414 kb)


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Xiao-Chun Yang
    • 1
  • Chong-Xing Tu
    • 1
  • Pei-Hua Luo
    • 1
  • Hong Zhu
    • 1
  • Di-Feng Zhu
    • 1
  • Hong-Hai Wu
    • 1
  • Xing-Lu Zhou
    • 1
  • Wei Lu
    • 2
  • Qiao-Jun He
    • 1
  • Bo Yang
    • 1
  1. 1.Institute of Pharmacology and Toxicology, College of Pharmaceutical SciencesZhejiang UniversityHangzhouPeople’s Republic of China
  2. 2.Shanghai Key Laboratory of Chemical BiologyEast China University of Science and TechnologyShanghaiPeople’s Republic of China

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