Zhang Shiwu, Li Man, Gu Yanjun, Liu Zhiyong, Xu Shaoyan, Cui Yanfeng, Sun Baocun
Department of Pathology, Tianjin Cancer Hospital, Tianjin, Medical University, Tianjin, 300060, PR China.
J Exp Clin Cancer Res. 2008 Nov 4;27(1):60. doi: 10.1186/1756-9966-27-60.
To observe the effects of thalidomide on melanoma tumor growth and blood supply patterns in C57 mice.
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.
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.
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.
观察沙利度胺对C57小鼠黑色素瘤肿瘤生长及血液供应模式的影响。
将30只皮下接种B16F10细胞的小鼠随机分为治疗组和对照组。治疗组于接种后第5天开始每天一次给予沙利度胺,剂量为200mg/kg,对照组给予等量的0.5%羧甲基纤维素。接种后每天测量肿瘤直径,直至第19天处死小鼠。经免疫组化和PAS组织化学双重染色后计数不同的血液供应模式。同时评估肿瘤组织中VEGF、NF-κB、PCNA、MMP-2和MMP-9的表达。
与对照组相比,治疗组的肿瘤体积(P = 0.019)、血管生成拟态数量(P = 0.03)和镶嵌血管数量(P = 0.004)均显著降低。治疗组VEGF(P = 0.004)、NF-κB(P = 0.009)、PCNA(P = 0.002)、MMP-2(P = 0.000)、MMP-9(P = 0.002)蛋白表达以及MMP-2(P = 0.000)和MMP-9(P = 0.000)mRNA均显著低于对照组。
沙利度胺通过调节血管生成因子抑制黑色素瘤中血管生成拟态通道和镶嵌血管的形成,并可诱导黑色素瘤细胞坏死,这可能与NF-κB信号通路有关。