Antimetastatic activity of MONCPT in preclinical melanoma mice model
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.
KeywordsMONCPT Metastasis Melanoma Antitumor
green fluorescent protein
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.