Journal
PIGMENT CELL & MELANOMA RESEARCH
Volume 25, Issue 5, Pages 630-638Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1755-148X.2012.01036.x
Keywords
melanoma; tumor; angiogenesis; vasculogenic mimicry; lycorine hydrochloride; VE-cadherin
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Funding
- National Natural Science Foundation of China [30971138]
- Chinese Academy of Science [XDA01040200]
- Suzhou City Scientific Research Funds [SWG0904, SS201004, SS201138]
- priority academic program development of Jiangsu Higher Education Institutions (PAPD)
- Cultivation Base of State Key Laboratory of Stem Cell and Biomaterials
- Jiangsu Province's Key Discipline of Medicine [XK201118]
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Melanoma cells actively participate in tumor angiogenesis and vasculogenic mimicry. However, anti-angiogenic therapy in patients with melanoma has not shown a significant survival gain. Thus, new anti-melanoma angiogenic and vasculogenic drugs are highly desired. Using the metastatic melanoma cell line C8161 as a model, we explored melanoma vasculogenic inhibitors and found that lycorine hydrochloride (LH) effectively suppressed C8161 cell-dominant formation of capillary-like tubes in vitro and generation of tumor blood vessels in vivo with low toxicity. Mechanistic studies revealed that LH markedly hindered expression of VE-cadherin in C8161 cells, but did not affect expression of six other important angiogenic and vasculogenic genes. Luciferase assays showed that LH significantly impeded promoter activity of the VE-cadherin gene in a dose-dependent manner. Together, these data suggest that LH inhibits melanoma C8161 cell-dominant vasculogenic mimicry by reducing VE-cadherin gene expression and diminishing cell surface exposure of the protein.
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