塞来昔布衍生物抑制剂CIH01对A549肺癌增殖及血管生成影响的实验研究

目的:探讨选择性环氧化酶-2(COX-2)抑制剂塞来昔布衍生物CIH01对A549肺癌移植瘤的抑制作用及其对肺瘤组织血管生成的影响。方法:建立裸鼠肺癌细胞株A549移植瘤模型,连续治疗20 d,于末次给药24 h后处死动物。每周测量2次肿瘤体积及动物体重,以末次各组瘤体积计算抑瘤率。采用Mtrigel Plug实验方法,连续治疗7 d后取出皮下胶块,进行HE染色,计算各组血管数平均值。结果:完成全部治疗后,CIH01组的平均肿瘤体积为(216±25)mm3,塞来昔布组的平均肿瘤体积(391±40)mm3,对照组的平均肿瘤体积为(633±92)mm3。CIH01的抑瘤率为64%,明显优于塞来昔布组,P0.05。各组Matrigel内的平均血管数分别为(2.82±0.71)、(7.90±2.83)、(10.75±3.11),与塞来昔布组及对照组比较,CIH01组的平均血管数均显著减少,P0.01。结论:CIH01对A549移植瘤模型有明显抑制作用,其作用机制之一与抑制肿瘤血管生成有关。

Experimental Study on the Effect of Celecoxib Derivatives Inhibitor CIH01 on the Proliferation of A549 Lung Cancer and the Angiogenesis

Objective: To evaluate the effects of celecoxib derivatives CIH01, the cyclooxygenase-2 (COX-2) selective inhibitor, on inhibiting A549 lung cancer xenograft and tumor angiogenesis. Methods: Established the tumor homograft model of lung cancer cell line A549 in nude mice, after 20 days treatment, the mice were sacrificed 24 hours after the last administration. Tumor volume and body weight were measured twice weekly and calculated tumor growth inhibition (TGI) using the last measurement. Then used Mtrigel plug assay, subcutaneous rubber blocks of all mice were removed and dyed by HE after 7 days treatment, calculated the number of vessels. Results: After the treatment, the average tumor volume of CIH01 group was (216±25) mm3, the mean tumor volume of celecoxib group was (391±40) mm3, and the mean tumor volume of control group was (633±92) mm3. The inhibition rate of CIH01 group (64%) was significantly higher than that of celecoxib group,P<0.05. And the average number of vessels of each group was (2.82±0.71), (7.90±2.83), and (10.75±3.11), the average number of vessels of celecoxib group reduced significantly than the celecoxib group and the control group, P<0.01. Conclusion: CIH01 has significant inhibitory effect on A549 tumor model, the mechanism of action is related to the inhibition of tumor angiogenesis.