Abstract:

Objective To investigate the expression of angiotensinⅡ (AngⅡ) in malignant melanoma cells and to explore the influence of AngⅡ on angiogenesis. Methods The expression of AngⅡ in the supernatant of A375 cells and primary human melanocytes was detected by radioimmunoassay. Human umbilical vein endothelial cells （HUVECs） were incubated with AngⅡ of 1 ?滋mol/L for 20 hours in an in vitro tube formation assay to observe the effects of AngⅡ on tube formation. A375 cells were incubated with angiotensinⅡ of 1 ?滋mol/L and losartan （an inhibitor of angiotensin II type 1 receptor, AT1R） of 1 ?滋mol/L, respectively for 24 hours; subsequently, reverse transcription PCR （RT-PCR） and enzyme-linked immunosorbent assay （ELISA）were carried out to measure the mRNA and protein expressions of vascular endothelial growth factor （VEGF） and basic fibroblast growth factor （bFGF）, respectively. Results The level of AngⅡ was 37.29 ± 0.27 pmol/L in the supernatant of A375 cells, significantly higher than that in the supernatant of normal human melanocytes (21.58 ± 0.32 pmol/L, P < 0.05）. AngⅡ apparently promoted the tube formation by HUVECs. Intact tubiform structures were formed by HUVECs in two-dimension matrigel after being treated with AngⅡ of 1 ?滋mol/L, with the area of tubiform structures being 2.5 ± 0.3 times that in the HUVECs treated with phosphate buffered solution （PBS） （P < 0.05）. The protein expressions of VEGF and bFGF in the supernatant of A375 cells and their mRNA expressions in A375 cells were significantly increased by AngⅡ, but suppressed by losartan （all P < 0.05）. Conclusions There is a local overexpression of AngⅡ in malignant melanoma, which can markedly promote angiogenesis. This may be one of the mechanisms by which the local renin-angiotensin system affects the initiation of malignant melanoma.