| First Author | Boolbol SK | Year | 1996 |
| Journal | Cancer Res | Volume | 56 |
| Issue | 11 | Pages | 2556-60 |
| PubMed ID | 8653697 | Mgi Jnum | J:33982 |
| Mgi Id | MGI:81462 | Citation | Boolbol SK, et al. (1996) Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis. Cancer Res 56(11):2556-60 |
| abstractText | Inducible cyclooxygenase (Cox-2), also known as prostaglandin H synthase 2 (PGH-2) is a key enzyme in the formation of prostaglandins and thromboxanes, Cox-2 is the product of an immediate-early gene that is expressed in response to growth factors, tumor promoters, or cytokines. Overexpression of Cox-2 is associated with both human colon cancers and suppression of apoptosis in cultured epithelial cells, an activity that is reversed by the nonsteroidal anti-inflammatory drug, sulindac sulfide, To address the relationship between Cox-2, apoptosis, and tumor development in vivo, we studied C57BL/6J-Min/+(Min) mice, a strain containing a fully penetrant dominant mutation in the Ape gene, leading to the development of gastrointestinal adenomas by 110 days of age, Min mice were fed AIN-76A chow diet and given sulindac (0.5 +/- 0.1 mg/day) in drinking water, Control Min mice and homozygous C57BL/6J-+/+ normal littermates lacking the Ape mutation (+/+) were fed AIN-76A diet and given tap water to drink, At 110 days of age, all mice were sacrificed, and their intestinal tracts were examined, Control Min mice had 11.9 +/- 7.8 tumors per mouse compared to 0.1 +/- 0.1 tumors for sulindactreated Min mice, As expected, +/+ littermates had no macroscopic tumors. Examination of histologically normal-appearing small bowel from Min animals revealed increased amounts of Cox-2 and prostaglandin E(2) compared to +/+ littermates, Using two different in situ techniques, terminal transferase-mediated dUTP nick end labeling and a direct immunoperoxidase method, Min animals also demonstrated a 27-47% decrease in enterocyte apoptosis compared to +/+ animals, Treatment with sulindac not only inhibited tumor formation but decreased small bowel Cox-2 and prostaglandin E, to baseline and restored normal levels of apoptosis, These data suggest that overexpression of Cox-2 is associated with tumorigenesis in the gastrointestinal epithelium, and that both are inhibited by sulindac administration. |
