Thalidomide influences growth and vasculogenic mimicry channel formation in melanoma.
OBJECTIVE
To observe the effects of thalidomide on melanoma tumor growth and blood supply patterns in C57 mice.


METHODS
Thirty mice inoculated subcutaneously with B16F10 cells were randomly divided into the treatment group and the control group. Thalidomide was administered once a day at a dose of 200 mg/kg for the treatment group starting on the fifth day after inoculation, and an equivalent volume of 0.5% carboxylmethyl cellulose was administered similarly in the control group. The diameter of the tumors was measured daily after inoculation until the mice were sacrificed on the 19th day. The different blood supply patterns were counted after immunohistochemical and PAS histochemical double-Staining. VEGF, NF-kappaB, PCNA, MMP-2 and MMP-9 expression in tumor tissue was also assessed.


RESULTS
The tumor volume(P = 0.019) and the number of vasculogenic mimicry(P = 0.03) and mosaic vessels(P = 0.004) in the treatment group were significantly decreased compared with the control group. VEGF(P = 0.004), NF-kappaB(P = 0.009), PCNA(P = 0.002), MMP-2 (P = 0.000), MMP-9(P = 0.002) protein expression and MMP-2(P = 0.000) and MMP-9(P = 0.000) mRNA in the treatment group were significantly lower than those in the control groups.


CONCLUSIONS
Thalidomide inhibits vasculogenic mimicry channel and mosaic vessels formation in melanoma through the regulation of vasculogenic factors, and it can induce necrosis of melanoma cells, which may be related with the NF-kappaB signaling pathway.
Zhang
Shiwu
S
Department of Pathology, Tianjin Cancer Hospital, Tianjin, Medical University, Tianjin, 300060, PR China. zhangshiwu666@yahoo.com.cn
Li
Man
M
Gu
Yanjun
Y
Liu
Zhiyong
Z
Xu
Shaoyan
S
Cui
Yanfeng
Y
Sun
Baocun
B
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008545:Melanoma / Q000098:blood supply* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013792:Thalidomide / Q000008:administration & dosage / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D013792:Thalidomide; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9