Hu P J, Yu J, Zeng Z R, Leung W K, Lin H L, Tang B D, Bai A H C, Sung J J Y
Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Gut. 2004 Feb;53(2):195-200. doi: 10.1136/gut.2003.021477.
Overexpression of cyclooxygenase 2 (COX-2) is frequently detected in gastric cancer and is believed to play a crucial role in gastric carcinogenesis.
We examined the chemopreventive effect of a COX-2 inhibitor in an animal model of stomach carcinogenesis.
Eighty six male Wistar rats were divided into six different treatment groups: group A, water alone (n = 5); group B, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG 100 micro g/ml) (n = 16); group C, indomethacin (3 mg/kg/day) (n = 16); group D, celecoxib (5 mg/kg/day) (n = 17); group E, celecoxib (10 mg/kg/day) (n = 16); and group F, celecoxib (20 mg/kg/day) (n = 16). Group B-F animals were treated with 10% sodium chloride (in the initial six weeks) and MNNG in drinking water to induce adenocarcinoma in the stomach. All animals received treatment for 40 weeks, and were sacrificed after death or at 48 weeks. Gastric neoplasm was evaluated by histology.
The incidences of gastric cancer were 0% in group A, 75% in group B, 68.8% in group C, 70.6% in group D, 18.8% in group E, and 31.3% in group F (p = 0.002, ANOVA). Compared with MNNG controls, treatment with celecoxib 10 mg/kg/day also showed lower tumour multiplicity (0.19 (0.40) v 1.00 (0.73); p = 0.004) and lower mean tumour volume (2.4 v 2805 mm(3); p = 0.02). Although tumours had significantly higher COX-2 expression than their adjacent normal tissues (p<0.02), there was no significant difference in COX-2 levels among tumours in the different treatment groups. The lowest tumour prostaglandin E(2) level was found in the indomethacin treated group, suggesting that the chemopreventive effect of celecoxib may be mediated by a COX independent pathway.
While treatment with indomethacin had no significant effect on tumour development, treatment with celecoxib reduced gastric cancer incidence and growth in rats.
环氧化酶2（COX - 2）的过表达在胃癌中经常被检测到，并且被认为在胃癌发生过程中起关键作用。
我们在胃癌发生的动物模型中研究了一种COX - 2抑制剂的化学预防作用。
86只雄性Wistar大鼠被分为六个不同的治疗组：A组，仅给予水（n = 5）；B组，给予N - 甲基 - N'-硝基 - N - 亚硝基胍（MNNG，100μg/ml）（n = 16）；C组，给予吲哚美辛（3mg/kg/天）（n = 16）；D组，给予塞来昔布（5mg/kg/天）（n = 17）；E组，给予塞来昔布（10mg/kg/天）（n = 16）；F组，给予塞来昔布（20mg/kg/天）（n = 16）。B - F组动物在最初六周用10%氯化钠处理，并在饮用水中给予MNNG以诱导胃腺癌。所有动物接受治疗40周，并在死亡后或48周时处死。通过组织学评估胃肿瘤。
A组胃癌发生率为0%，B组为75%，C组为68.8%，D组为70.6%，E组为18.8%，F组为31.3%（p = 0.002，方差分析）。与MNNG对照组相比，给予10mg/kg/天塞来昔布治疗还显示出较低的肿瘤多发性（0.19（0.40）对1.00（0.73）；p = 0.004）和较低的平均肿瘤体积（2.4对2805mm³；p = 0.02）。尽管肿瘤的COX - 2表达明显高于其相邻正常组织（p<0.02），但不同治疗组肿瘤之间的COX - 2水平没有显著差异。在吲哚美辛治疗组中发现肿瘤前列腺素E₂水平最低，这表明塞来昔布的化学预防作用可能由COX非依赖性途径介导。
虽然吲哚美辛治疗对肿瘤发展没有显著影响，但塞来昔布治疗可降低大鼠胃癌的发生率和生长。
