塞莱昔布对结肠癌细胞生长及肝转移瘤血管生长因子表达的影响

Effects of celecoxib on cell proliferation and expression of vascular endothelial growth factor in colonic cancer with hepatic metastasis

目的:探讨塞莱昔布对体外培养的结肠癌细胞生长及肝转移瘤模型血管生长因子(VEGF)表达的影响.方法:以人结肠癌细胞株HT-29,HCT-116为对象,体外药物敏感实验(MTT)法检测塞莱昔布对肿瘤细胞的增殖抑制效应,流式细胞术检测肿瘤细胞各细胞周期分布变化情况,肿瘤细胞接种裸鼠,观察肝转移瘤VEGF表达情况.结果:塞莱昔布对人结肠癌细胞株生长的抑制作用呈时间、剂量依赖性效应,且对HT-29细胞作用强于HCT-116细胞(P<0.01);塞莱昔布可改变结肠癌细胞株细胞周期的分布,明显降低增殖指数(P<0.05).塞莱昔布具有明显的抑制肝转移瘤VEGF表达的作用(P=0.00).结论:塞莱昔布可通过抑制COX-2酶活性而抑制肿瘤细胞的分裂和增殖,诱导其凋亡,并抑制肿瘤血管生成,干预结肠癌的转移与复发.

AIM： To explore the role of celecoxib in the proliferation and cycle distribution of colon cancer cells cultured in vitro as well as its effect on the expression of vascular endothelial growth factor （VEGF） in the animal model of colon cancer with hepatic metastasis. METHODS： The human colon cancer cells HT-29 and HCT-116 were employed in the study. After treatment with celecoxib, the inhibitory effect of celecoxib on the proliferation of cancer cells was determined by MTT assay, and the ceil cycle distribution was detected by flow cytometry. The tumor cells were inoculated in the nude mice, and the expression of VEGF in the model was detected by immunohistochemistry. RESULTS： Celecoxib inhibited the proliferation of the tumor cells in a time- and dose-dependent manner. The inhibitory effect on HT-29 cells was stronger than that on HCT-116 cells （P 〈0.01）. Celecoxib changed the cell cycle distribution of both cells, and decreased the proliferation index of cells obviously （P 〈0.05）. Celecoxib significantly inhibited the expression of VEGF in the animal model of colon cancer with hepatic metastasis （P = 0.00）. CONCLUSION： Celecoxib can inhibit the division and proliferation of the tumor cells through inhibiting the activity of COX-2, consequently it play an important role in the prevention of hepatic metastasis and relapse of colon cancer.