白细胞介素-18对Lewis肺癌小鼠肿瘤增殖及微血管生成的抑制作用

Inhibition effect of IL-18 on proliferation of tumor cells and angiogenesis in C57BL/6 mice Lewis lung cancer

背景与目的:白细胞介素18(interleukin18,IL-18)是新近发现的一种多效能细胞因子,在抗肿瘤、免疫调节等方面有着积极的作用及潜在广阔的应用前景。本文旨在研究IL-18对Lewis肺癌小鼠肿瘤增殖及微血管生成的抑制作用。方法:复制Lewis肺癌小鼠模型16只,随机均分为IL-18治疗组(A组)与荷瘤模型组(B组),分别于接种第7天起予IL-18、0.9%氯化钠溶液腹腔注射,每日1次,连续7次。观察Lewis肺癌小鼠健康状况,监测皮下移植瘤变化,并用免疫组化法检测肿瘤增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)与微血管密度(microvessel density,MVD)表达水平。结果:IL-18对小鼠健康状况无明显影响,但可明显抑制移植瘤生长,抑瘤率为75%,并显著降低肿瘤PCNA表达与MVD水平,IL-18治疗组与荷瘤模型组该两项指标比较,差异均有统计学意义(P<0.01)。结论:IL-18可抗Lewis肺癌生长,其作用与抑制肿瘤增殖活性及微血管生成相关。

Background and purpose： IL-18 is one of the latest discoveries of pleiotropic cytokine, which can play an active role in antitumor and immunoregulation, and there might be a variety of potentialities of its application. This study was to investigate the inhibition effect of IL-18 on proliferation and angiogenesis of tumor cells in C57BL/6 mice Lewis lung cancer. Methods： C57BL/6 mice engrafted with Lewis lung cancer was used as animal model, The expression level of proliferating cell nuclear antigen（PCNA） and microvessel density （MVD） in tumor mass were measured by imunohistochemistry staining（IHCS）. Results： IL-18 could obviously inhibit the growth of tumor cells and decelerate the proliferation of tumor cells by 75%, and reduce the expression of PCNA and MVD[（16±4） vs （25±4）] in the xenografts but not in normal animals. Conclusion： IL-18 could inhibit tumor growth in C57BL/6 mice Lewis lung cancer model, down regulate proliferating activity of tumor cells, and its inhibition of angiogenesis may be one its important mechanisms.