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沙利度胺对小鼠恶性黑色素瘤生长及血管生成模式的影响

李莘1,赵秀兰2,张丹芳2,齐丽莎3   

  1. 1. 天津市海河医院病理科
    2.
    3. 天津医科大学附属肿瘤医院
  • 收稿日期:2010-04-26 修回日期:2010-06-18 出版日期:2010-12-15 发布日期:2010-12-15
  • 通讯作者: 李莘

Thalidomide influence the growth and angiogenesis patterns of melanoma

  • Received:2010-04-26 Revised:2010-06-18 Published:2010-12-15 Online:2010-12-15

摘要: 目的:观察沙利度胺对恶性黑色素瘤(恶黑)生长及血管生成模式的影响,为对其治疗提供实验依据。方法:B16黑色素瘤移植瘤模型C57小鼠35只,随机分为实验组20只,对照组15只,分别给予沙利度胺及0.5%羧甲基纤维素钠溶液灌胃。计数肿瘤组织中内皮依赖性血管、马赛克血管和血管生成拟态数目及肿瘤细胞坏死情况,并进行血管内皮细胞生长因子(VEGF)、核因子(NF)-κB、基质金属蛋白酶(MMP)-2、MMP-9和增殖细胞核抗原(PCNA)的免疫组化染色。结果:给药9d后,实验组小鼠的肿瘤体积明显小于对照组(P<0.05)。实验组内皮依赖性血管、马赛克血管和血管生成拟态数量显著低于对照组(P<0.05),且实验组VEGF、NF-κB、PCNA、MMP-2及MMP-9的表达也明显低于对照组(P<0.05)。实验组肿瘤组织中坏死细胞数明显高于对照组(P<0.05)。结论:沙利度胺可以抑制恶黑血管生成,促进肿瘤细胞的坏死,抑制肿瘤的生长。 

关键词: 沙利度胺, 黑色素瘤, 血管生成拟态, 马赛克血管, 内皮依赖性血管, NF-κB

Abstract: OBJECTIVE: The aim of this research was to examine the influence of thalidomide on the growth and angiogenesis of melanoma. These results would be hoped to elicit a novel approach to the clinical treatment of melanoma. METHODS: Thirty-five C57 mice of the melanoma transplanted model was lavage by thalidomide and 0.5% CMC. The vasculogenic mimicry, mosaic vessel, endothelial dependent vessel and necrosis ratio of tumor were measured by H&E staining. The expression level of MMP-2, MMP-9, VEGF, NF-κB and PCNA were examined by immunohistochemistry. RESULTS: The tumor volume of experiment group was statistically significantly decreased compared with the control group(P<0.05). The vasculogenic mimicry, mosaic vessel and endothelial dependent vessel count in experiment group were statistically significantly decreased compared with the control group(P<0.05). The necrosis ratio of tumor was increased compared with the control group(P<0.05). The expression level of MMP-2, MMP-9, VEGF, NF-κB and PCNA of experiment group tumor tissues were statistically significantly decreased compared with the control group(P<0.05). CONCLUSIONS: Thalidomide could inhibit the vasculogenic mimicry, mosaic vessel and endothelial dependent vessel information, induce necrosis to inhibit tumor growth.

Key words: Thalidomide, Melanoma, Vasculogenic mimicry, Mosaic vessel, Endothelial dependent vessel, NF-κB