Therapeutic utility of aspirin in the ApcMin/+ murine model of colon carcinogenesis.
Therapeutic utility of aspirin in the ApcMin/+ murine model of colon carcinogenesis.
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DOI：
10.1186/1471-2407-2-19
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发表时间：
2002-08-09
期刊：
影响因子：
3.8
通讯作者：
Miller MJ
中科院分区：
文献类型：
--
作者：
Reuter BK;Zhang XJ;Miller MJ
近年来，非甾体类抗炎药，特别是阿司匹林已成为一类潜在的癌症化疗药物。尽管从流行病学、临床和动物研究中获得了丰富的知识，但阿司匹林治疗已确诊的胃肠道癌症的有效性尚未确定。本研究检查了阿司匹林治疗Min/+小鼠中已建立的息肉病的能力。从12-16周龄开始，每天一次用药物媒介物或阿司匹林（25 mg/kg）经口治疗具有已建立的息肉病的Min/+小鼠。治疗结束后，确定肠道肿瘤的数量、位置和大小。检查的其他变量是肿瘤内凋亡细胞的数量和考克斯活性。与溶剂处理的Min/+小鼠相比，Min/+小鼠给予阿司匹林4周对肿瘤数量无影响（分别为65 ± 8 vs. 63 ± 9）。此外，阿司匹林对肿瘤的大小或位置没有影响。然而，阿司匹林治疗使肿瘤内凋亡阳性细胞的数量增加了2倍以上（p < 0.05），并显著降低了肝脏PGE 2含量。发现阿司匹林对已建立息肉病的Min/+小鼠给药时，对肿瘤数量和大小没有影响。本研究的发现质疑阿司匹林作为一种独立治疗已确诊的胃肠道癌症的效用。然而，阿司匹林显著促进细胞凋亡的能力可能使其适用于联合化疗。
In recent years it has become evident that nonsteroidal anti-inflammatory drugs, in particular aspirin represent a potential class of cancer chemotherapeutic agents. Despite the wealth of knowledge gained from epidemiological, clinical and animal studies, the effectiveness of aspirin to treat established gastrointestinal cancer has not been determined. The present study examines the ability of aspirin to treat established polyposis in Min/+ mice. Min/+ mice with established polyposis were treated orally once daily from 12–16 weeks of age with either drug vehicle or aspirin (25 mg/kg). Upon completion of treatment, the number, location and size of intestinal tumours was determined. Additional variables examined were the number of apoptotic cells within tumours and COX activity. Administration of aspirin for 4 weeks to Min/+ mice produce no effect on tumour number compared to vehicle-treated Min/+ mice (65 ± 8 vs. 63 ± 9, respectively). In addition, aspirin had no effect on tumour size or location. However, aspirin treatment produced a greater than 2-fold (p < 0.05) increase in the number of apoptotic positive cells within tumours and significantly decreased hepatic PGE2 content. Aspirin was found to have no effect on tumour number and size when administered to Min/+ mice with established polyposis. The findings in the present study call in to question the utility of aspirin as a stand-alone treatment for established GI cancer. However, aspirin's ability to significantly promote apoptosis may render it suitable for use in combinatorial chemotherapy.
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影响因子：
158.5
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