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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(P<0.05),低剂量组略有减低但差异无统计学意义(P>0.05)。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。
OBJECTIVE: To investigate the effects of celecoxib at different dosages on the growth, COX-2 expression and lymphatic vessel density in C57BL / 6 mice and to investigate the possible mechanism of celecoxib on lymphangiogenesis in C57BL / 6 mice Mechanism of action and dose-effect relationship. Methods: Lewis lung carcinoma cell lines were inoculated subcutaneously in the left inguinal of C57BL / 6 mice to establish a transplanted tumor model. They were randomly divided into 4 groups: control group, celecoxib low dose, middle dose and high dose groups. The survival status and tumor volume of tumor-bearing mice were observed. After 42 days, mice were sacrificed and the expression of COX-2 and lymphatic vessel density were detected by western blot. Results: Semiquantitative Western blot showed that the expression of COX-2 in high and middle doses of celecoxib and the density of lymphatic vessels in immunohistochemical staining were significantly decreased (P <0.05) The group was slightly reduced but the difference was not statistically significant (P> 0.05). The degree of inhibition was significantly dose-dependent. CONCLUSION: Celecoxib inhibits the growth and lymphatic metastasis of Lewis lung carcinomas, which may be related to the down-regulation of the expression of COX-2, the inhibition of lymphangiogenesis signaling pathway and the inhibition of lymphangiogenesis, with a dose-dependent manner Sex.