Therapeutic utility of aspirin in the ApcMin/+ murine model of colon carcinogenesis.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Reuter
Brian K
BK
Center for Cardiovascular Sciences, Albany Medical College, New York 12208, USA. ok_go@hotmail.com
Zhang
Xiao-Jing
XJ
Miller
Mark J S
MJ
D011125:Adenomatous Polyposis Coli / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D001241:Aspirin / Q000627:therapeutic use*; D017491:Genes, APC; D051379:Mice; D008810:Mice, Inbred C57BL; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin