塞来昔布对膀胱癌细胞移植小鼠的治疗作用及机制

Therapeutic effect and mechanism of celecoxib on bladder cancer cell implanted mice

目的初步探讨塞来昔布对膀胱癌细胞移植小鼠的治疗作用及相关机制。方法将60只雄性BALB/c裸鼠随机分为3组:对照组、模型组及观察组。模型组及观察组利用注射人膀胱癌细胞系5637制备小鼠膀胱癌模型。观察组小鼠给予塞来昔布治疗,对照组及模型组小鼠给予同剂量0.9%氯化钠溶液。治疗4周后,取模型组和实验组小鼠瘤组织及对照组正常组织,检测3组小鼠组织中CD4^+、CD8^+表达量及CD4^+/CD8^+比值;利用Western blot检测COX-2、VEGF及cPLA2阳性表达;利用TUNEL法检测模型组及观察组小鼠肿瘤细胞凋亡率。结果对照组小鼠正常生长,皮下无肿瘤生成。模型组和观察组小鼠成瘤率100%。模型组和观察组小鼠的瘤体质量分别为(2.08±0.36)g和(1.18±0.21)g,与模型组相比,观察组小鼠瘤体质量显著降低(P<0.05)。观察组小鼠的肿瘤抑制率为43.33%。模型组及观察组小鼠移植瘤中CD4^+、CD4^+/CD8^+水平均显著低于对照组,CD8+水平均显著高于对照组(P<0.05)。观察组小鼠瘤组织中CD4^+、CD4^+/CD8^+水平明显高于模型组,CD8+水平明显低于模型组(P<0.05)。COX-2及cPLA2蛋白在对照组小鼠组织中不表达,VEGF蛋白在3组中均有阳性表达。观察组小鼠中COX-2、VEGF及cPLA2蛋白表达水平明显低于模型组,细胞凋亡指数明显高于模型组小鼠(P<0.05)。结论塞来昔布对小鼠膀胱癌具有一定的抑制作用,其作用机制可能与提高膀胱癌小鼠免疫系统水平、减轻炎性反应、促进癌细胞凋亡有关。

Objective To explore the therapeutic effect of celecoxib on mice implanted with bladder cancer cells and its related mechanism.Methods Sixty male BALB/c nude mice were randomly divided into three groups:control group,model group and observation group.The model group and the observation group were implanted with human bladder cancer cell line 5637 to establish a mouse bladder cancer model.The mice in the observation group were treated with celecoxib,while the mice in the control group and the model group were injected with the same dose of 0.9%sodium chloride solution.After 4 weeks of treatment,the tumor tissue of model group and experimental group and normal tissue of control group were taken to detect the expression of CD4^+,CD8^+,and the ratio of CD4^+/CD8^+ in the tissues of three groups.Western blot was performed to test the positive expression of COX-2,VEGF and cPLA2.TUNEL method was used to test the apoptotic rate of bladder cancer cells in model group and observation group.Results The mice in the control group grew normally without tumor under the skin.The tumorigenesis rate of model group and observation group was 100%.The tumor mass of the model group and the observation group were(2.08±0.36)g and(1.18±0.21)g.Compared with the model group,the tumor mass of mice in the observation group decreased significantly(P<0.05).The tumor inhibition rate of mice in the observation group was 43.33%.The levels of CD4^+,CD4^+/CD8^+ in tissue of model group and observation group was significantly lower than that of control group,and the level of CD8^+ was significantly higher than that of control group(P<0.05).The levels of CD4^+,CD4^+/CD8^+ in tumor tissue of mice in the observation group were significantly higher than those in the model group,and the level of CD8+was significantly lower than that in the model group(P<0.05).COX-2 and cPLA2 protein levels were not expressed in tissues of mice in control group,the expression of VEGF protein was positive in all three groups.The expression levels of COX-2,VEGF and cPLA2 in the observation group were significantly lower than those in the model group,and the apoptotic index was significantly higher than that in the model group(P<0.05).Conclusions Celecoxib has a certain inhibitory effect on implanted bladder cancer in mice.Its mechanism may be related to improving the immune system level of bladder cancer mice,alleviating inflammatory reaction and inducing cancer cell apoptosis.