Inhibitory effect of norcantharidin on melanoma tumor growth and vasculogenic mimicry by suppressing MMP-2 expression

Abstract

A form of microcirculation called vasculogenic mimicry (VM), which constitutes a novel approach for tumor blood supply in certain highly aggressive malignant tumors, was recently reported to contribute to tumor metastasis and poor prognosis in melanoma patients. Development of strategies to target tumor VM may be significant to reduce the recurrence and metastasis of melanoma. Norcantharidin (NCTD) has been shown to inhibit tumor growth and VM of human gallbladder carcinomas. Besides, NCTD could induce melanoma cell apoptosis. However, whether NCTD can inhibit the growth and VM formation of melanoma has not been evaluated. The present study aims to investigate the anti-VM activity of NCTD as a VM inhibitor for melanoma and its potential mechanisms. The anti-VM activity of NCTD was determined in human melanoma A375 cells and xenografts in vitro and in vivo. The findings indicate that NCTD inhibits tumor growth and VM formation of melanoma both in vitro and in vivo by suppressing matrix metalloproteinase-2 expression. The results suggest that NCTD is a potential therapeutic agent targeting VM in melanoma.