不同剂量的塞来昔布对C57BL/6小鼠移植瘤微淋巴管密度抑制作用的研究(英文)

目的:观察不同剂量的塞来昔布对C57BL/6小鼠肺癌移植瘤生长、COX-2表达和微淋巴管密度影响,探讨塞来昔布对C57BL/6小鼠肺癌移植瘤淋巴管生成可能作用机制及量效关系。方法:将Lewis肺癌细胞株接种于C57BL/6小鼠左侧腹股沟皮下建立移植瘤模型,随机分为4组:对照组、塞来昔布低剂量、中剂量、高剂量组。观察荷瘤小鼠生存状态,瘤体积变化,种瘤42天后牺牲小鼠,western blot半定量检测COX-2表达及微淋巴管密度。结果:Western blot半定量显示:塞来昔布高、中剂量组COX-2的表达水平及免疫组织化学染色微淋巴管密度计数均明显减低,差异有统计学意义(P0.05),低剂量组略有减低但差异无统计学意义(P0.05)。抑制程度呈明显的剂量依赖性。结论:塞来昔布抑制Lewis肺癌移植瘤的生长及淋巴转移,可能与下调COX-2的表达,阻遏了淋巴管生成的信号通路,抑制微淋巴管生成有关,该抑制作用呈一定的剂量相关性。

The Inhibitory Effect of Different Doses of Celecoxib on Lymphatic Microvessel Density in Tumor Homografts in C57BL/6 Mice

Objective:To observe the effects of different doses of celecoxib on the growth of tumor homografts in C57BL/6 mice, COX-2 expression and lymphatic microvessel density and to explore the possible mechanism of action and dose-effect relationship of celecoxib on lymphangiogenesis of Lewis lung tumor.Methods:The cell lines of Lewis lung carcinoma were inoculated in the left inguinal subcutis of C57BL/6 mice for establishment of the tumor homograft model. They were randomly divided into four groups, including the control group, low-dose, medium-dose and high-dose celecoxib groups. The survival status and tumor volume change were observed in tumor-bearing mice. The mice were sacrificed 42 days after transplantation of tumors. The tumor tissue was collected for western blot semi-quantitative detection of COX-2 expression and lymphatic microvessel density (LMVD).Results:Semi-quantitative western blot determination showed that the expression levels of COX-2 and immunohistochemical-stained lymphatic microvessel density counting in the high- and medium-dose groups were significantly reduced, and the differences were statistically significant (P<0.05); the low-dose group was slightly reduced but not significantly different (P>0.05). The degree of inhibition was in a dose-dependent manner.Conclusion:The inhibition of celecoxib on the growth of Lewis lung cancer homografts and lymph node metastasis may be related to the down-regulation of COX-2 expression, repression of lymphangiogenesis signaling pathways, and inhibition of lymphangiogenesis which is related to dosage.