Ibuprofen inhibits colitis-induced overexpression of tumor- related Rac1b

Paulo Matos, Larissa Kotelevets, Vânia Gonçalves, Andreia Henriques, Philippe Zerbib, Mary Pat Moyer, Eric Chastre, Peter Jordan

Producción científica: Articlerevisión exhaustiva

30 Citas (Scopus)

Resumen

The serrated pathway to colorectal tumor formation involves oncogenic mutations in the BRAF gene, which are sufficient for initiation of hyperplastic growth but not for tumor progression. A previous analysis of colorectal tumors revealed that overexpression of splice variant Rac1b occurs in around 80% of tumors with mutant BRAF and both events proved to cooperate in tumor cell survival. Here, we provide evidence for increased expression of Rac1b in patients with inflamed human colonic mucosa as well as following experimentally induced colitis in mice. The increase of Rac1b in the mouse model was specifically prevented by the nonsteroidal anti-inflammatory drug ibuprofen, which also inhibited Rac1b expression in cultured HT29 colorectal tumor cells through a cyclooxygenase inhibition-independent mechanism. Accordingly, the presence of ibuprofen led to a reduction of HT29 cell survival in vitro and inhibited Rac1b-dependent tumor growth of HT29 xenografts. Together, our results suggest that stromal cues, namely, inflammation, can trigger changes in Rac1b expression in the colon and identify ibuprofen as a highly specific and efficient inhibitor of Rac1b overexpression in colorectal tumors. Our data suggest that the use of ibuprofen may be beneficial in the treatment of patients with serrated colorectal tumors or with inflammatory colon syndromes.

Idioma originalEnglish (US)
Páginas (desde-hasta)102-111
Número de páginas10
PublicaciónNeoplasia (United States)
Volumen15
N.º1
DOI
EstadoPublished - ene 2013
Publicado de forma externa

ASJC Scopus subject areas

  • Cancer Research

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