肺瘤平膏及其联合塞来昔布干预时间对Lewis肺癌小鼠不同肿瘤微环境中COX-2表达的影响

Effects of Feiliuping Ointment and combined with Celecoxib on the expression of COX-2 in different tumor microenvironment on mice with lewis lung carcinoma

目的:观察肺瘤平膏及其联合塞来昔布对癌组织(肿瘤核心微环境)与非癌组织(转移微环境)中环氧合酶-2(COX-2)表达的影响,揭示中药干预时间对不同肿瘤微环境中关键炎性分子的作用优势。方法:建立Lewis肺癌移植瘤小鼠模型,分别在肺瘤平膏干预14、21、28d收集瘤体、肺组织,并通过免疫组化、Western blotting方法检测COX-2的表达。结果:肿瘤核心微环境中:与对照组相比,14d时,各组瘤体COX-2的表达明显降低,28d时,各组瘤体COX-2的表达无明显变化。肿瘤转移微环境中:与对照组比较,21d时,肺瘤平膏可明显抑制COX-2的表达(P<0.05),28d时,抑制COX-2的作用增强(P<0.01);肺瘤平膏联合塞来昔布在各阶段均可以抑制COX-2的表达,并且其抑制作用随时间不断增强。结论:长时间应用肺瘤平膏对转移微环境中COX-2关键分子的调控作用优于对肿瘤核心微环境,其联合塞来昔布具有协同或者叠加作用。

Objective： To reveal the superiority of intervention time of TCM to the key inflammatory molecules in different tumor micro-environment by observing the expression of COX-2 in carcinoma tissues （the core tumor micro- environment） and non-carcinoma tissues （metastasis micro-environment） which was treated by Feiliuping （FLP） ointment combined with Celecoxib. Methods： After establishing the lewis lung carcinoma mice model, the expression of COX-2 was detected in the tumor and lung tissue at 14th, 21th and 28th day by immunohistochemistry and Western blotting. Results： Compared with the control group, the expression of COX-2 of each group was decreased significantly at 14th day, while there was no obvious change at 28th day in the core micro-environment. In the metastasis micro-environment, compared with the control group, FLP ointment significantly increased the expression of COX-2 （P〈0.05） at 21th day, and it increased the inhibition of the expression of COX-2 at 28th day （P〈0.01）. FLP ointment combined with Celecoxib could inhibite the expression of COX-2 at every stage, with the inhibition strengthened as the inhibiton time. Conclusion： It is superior to use a long-time FLP ointment by regulating the key molecule COX-2 in the metastasis micro-environment than in the core micro-environment, which has synergistic or addictive effect combined with Celecoxib.