Journal Article

Sulindac effects on inflammation and tumorigenesis in the intestine of mice with <i>Apc</i> and <i>Mlh1</i> mutations

Osamu Itano, Kan Yang, Kunhua Fan, Naoto Kurihara, Hiroharu Shinozaki, Sadanori Abe, Bo Jin, Claudia Gravaghi, Winfried Edelmann, Leonard Augenlicht, Levy Kopelovich, Raju Kucherlapati, Sergio Lamprecht and Martin Lipkin

in Carcinogenesis

Volume 30, issue 11, pages 1923-1926
Published in print November 2009 | ISSN: 0143-3334
Published online September 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp200
Sulindac effects on inflammation and tumorigenesis in the intestine of mice with Apc and Mlh1 mutations

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

We have previously reported that sulindac, a non-steroidal anti-inflammatory drug, inhibited tumor formation in the small intestine but increased tumors in the colon of ApcMin/+ mice, a model of human familial adenomatous polyposis. To further explore intestinal regional responses, we studied effects of sulindac on additional gene-targeted mouse models of human intestinal tumorigenesis; these were (i) Apc1638N/+ mouse (chain termination mutation in exon 15 of the Apc gene); (ii) Mlh1+/− mouse (DNA mismatch repair deficiency, a mouse model of human hereditary non-polyposis colorectal cancer) and (iii) double-heterozygous Mlh1+/−Apc1638N/+ mutant mouse. Mice were fed AIN-76A control diet with or without 0.02% sulindac for 6 months. Intestinal regional tumor incidence, multiplicity, volume and degree of inflammation were used as end points. The results showed the following: (i) sulindac inhibited tumor development in the small intestine of Apc1638N/+ mice; (ii) in contrast, sulindac increased tumors in the small intestine of Mlh1 mutant mice, a neoplastic effect which persisted in heterozygous compound Mlh1+/−Apc1638N/+ mutant mice; (iii) sulindac increased tumors in the cecum of all mice regardless of genetic background; (iv) sulindac decreased inflammation in the small intestine of Apc1638N/+ mice, but it increased inflammation in the small intestine of Mlh1+/ mice and Mlh1+/−Apc1638N/+ mice and (v) sulindac enhanced inflammation in the cecum of all mutant mice. Findings indicate that the effects of sulindac in the intestine of these mutant mouse models are probably related to genetic background and appear to be associated with its inflammatory-inducing response.

Journal Article.  2865 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.