摘要
目的探讨阿司匹林对结肠炎相关结直肠癌(CAC)小鼠模型的肿瘤形成、肿瘤细胞凋亡以及肠道炎症的影响。方法将60只雄性Balb/c小鼠随机分为模型组、治疗组和对照组各20只。模型组和治疗组采用致癌剂氧化偶氮甲烷(AOM)联合致炎症试剂右旋糖酐硫酸钠(DSS)诱导建立小鼠CAC模型,治疗组从实验开始给予阿司匹林200mg/kg直至实验结束;对照组无任何处理。造模第80天,取结肠组织行病理学检测,采用TUNEL法检测肿瘤细胞的凋亡,ELISA法检测肿瘤坏死因子α(TNF-α)和髓过氧化物酶(MPO)的表达。结果治疗组肠道炎症评分、肿瘤数量、肿瘤直径、TNF-α及MPO表达分别为2.38±0.92、4.17±2.32、(3.18±2.07)mm、(39.69±7.27)pg/mg和(3.32±1.29)pg/mg,与模型组的2.5±0.93、6.33±3.16、(5.38±2.28)mm、(42.68±8.13)pg/mg和(3.56±1.24)pg/mg比较,差异均无统计学意义(P>0.05)。治疗组、模型组和对照组小鼠的凋亡率分别为(15.92±3.26)%、(7.31±1.27)%和(3.70±1.65)%,差异具有统计学意义;治疗组凋亡指数为1.7±0.38,显著高于模型组的0.95±0.21(P=0.01)。结论阿司匹林能够显著促进CAC小鼠模型结直肠癌细胞的凋亡,但对肠道炎症无明显影响,因而在CAC防治方面可能存在潜在的临床应用价值。
Objective To explore the effects of aspirin on colitis, tumorigenesis and tumor cells apoptosis in a murine model of colitis-associated colorectal cancer （CAC）. Methods Balb/c mice were randomized into three groups. Mice in model group and treatment group were given azoxymethane （AOM） and dextran sodium sulfate （DSS） for inducing CAC, and mice in treatment group were treated with aspirin（5001xg/d） , while wild type Balb/c mice were considered as the control. Mice were sacrificed on day 80 of the experiment, and the large bowel tissue was collected and investigated by histopathology. Terminal deoxynucleotidyl transferase de- oxyuridine triphosphate nick end labeling （TUNEL） and the apoptotic index （AI） assay was used to detect the tumor cells apoptosis in colorectal cancer in different groups. Additionally, the levels of TNF-α and MPO in CAC tissue were assessed by ELISA method. Re- sults It was found that regardless of aspirin administration, all mice treated with AOM/DSS developed tumors （6. 33 ± 3.16 vs. 4. 17 ± 2.32, P 〉 0. 05 ） , and tumor size was （5.38± 2. 28 ） mm vs. （ 3. 18 ± 2. 07 ） mm （ P 〉 0. 05 ） between model group and treatment group. There was no statistically difference between groups plus or not plus aspirin in the intestinal inflammation in the murine model of CAC （ inflammatory score ： 2. 38 _± 0. 92 vs. 2. 5 ±0. 93, P 〉 0. 05 ）. Additionally, there were no differences in the levels of TNF-α （39.69±7.27 vs. 42. 68 ±8.13 pg/mg, P〉0.05） and MPO （3.32±1.29 vs. 3.56±1.24 pg/mg, P〉0.05） between model group and treatment group. It was apparent that specimens from treatment group had comparatively greater mean AI than those from model group （ 1.7 ± 0. 38 vs. 0. 95 ±0. 21, P = 0. 01 ） , which was confirmed also by TUNEL staining. Conclusion Aspirin can pro- mote tumor cells apoptosis in a murine model of CAC, but not relate to intestinal inflammation, which has a potential clinical value inthe prevention and treatment of colorectal cancer.
出处
《临床肿瘤学杂志》
CAS
2012年第12期1062-1065,共4页
Chinese Clinical Oncology
关键词
阿司匹林
结肠炎相关结直肠癌
凋亡
肿瘤发生
Aspirin
Colitis-associated colorectal cancer （CAC）
Apoptosis
Carcinogenesis
