Ibuprofen inhibits colitis-induced overexpression of tumor-related Rac1b
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.18/1200 |
Resumo: | 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. The analysis of colorectal tumors revealed that overexpression of splice variant Rac1b occurs in around 80% of tumors with mutant B-Raf and both events were shown to cooperate in tumor cell survival. Here we provide evidence for increased expression of Rac1b in samples from inflammatory bowel disease patients as well as following experimentally induced colitis in mice. The increase of Rac1b in the mouse model was specifically prevented by the non-steroidal anti-inflammatory drug ibuprofen, which also inhibited Rac1b expression in cultured HT29 colorectal tumour 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 and in cancer prophylaxis following colon inflammation disorders. |
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Ibuprofen inhibits colitis-induced overexpression of tumor-related Rac1bVias de Transdução de Sinal e Patologias AssociadasRac1bCancro ColorectalDoença Inflamatória do IntestinoNSAIDIbuoprofenThe 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. The analysis of colorectal tumors revealed that overexpression of splice variant Rac1b occurs in around 80% of tumors with mutant B-Raf and both events were shown to cooperate in tumor cell survival. Here we provide evidence for increased expression of Rac1b in samples from inflammatory bowel disease patients as well as following experimentally induced colitis in mice. The increase of Rac1b in the mouse model was specifically prevented by the non-steroidal anti-inflammatory drug ibuprofen, which also inhibited Rac1b expression in cultured HT29 colorectal tumour 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 and in cancer prophylaxis following colon inflammation disorders.Neoplasia PressRepositório Científico do Instituto Nacional de SaúdeMatos, PauloKotelevets, LarissaGonçalves, VâniaHenriques, AndreiaZerbib, PhilipeMoyer, Mary AnnChastre, EricJordan, Peter2013-02-08T14:33:13Z2013-012013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/1200engNeoplasia. 2013 Jan;15(1):102-111522-8002info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:38:37Zoai:repositorio.insa.pt:10400.18/1200Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:36:21.888624Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Ibuprofen inhibits colitis-induced overexpression of tumor-related Rac1b |
title |
Ibuprofen inhibits colitis-induced overexpression of tumor-related Rac1b |
spellingShingle |
Ibuprofen inhibits colitis-induced overexpression of tumor-related Rac1b Matos, Paulo Vias de Transdução de Sinal e Patologias Associadas Rac1b Cancro Colorectal Doença Inflamatória do Intestino NSAID Ibuoprofen |
title_short |
Ibuprofen inhibits colitis-induced overexpression of tumor-related Rac1b |
title_full |
Ibuprofen inhibits colitis-induced overexpression of tumor-related Rac1b |
title_fullStr |
Ibuprofen inhibits colitis-induced overexpression of tumor-related Rac1b |
title_full_unstemmed |
Ibuprofen inhibits colitis-induced overexpression of tumor-related Rac1b |
title_sort |
Ibuprofen inhibits colitis-induced overexpression of tumor-related Rac1b |
author |
Matos, Paulo |
author_facet |
Matos, Paulo Kotelevets, Larissa Gonçalves, Vânia Henriques, Andreia Zerbib, Philipe Moyer, Mary Ann Chastre, Eric Jordan, Peter |
author_role |
author |
author2 |
Kotelevets, Larissa Gonçalves, Vânia Henriques, Andreia Zerbib, Philipe Moyer, Mary Ann Chastre, Eric Jordan, Peter |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Matos, Paulo Kotelevets, Larissa Gonçalves, Vânia Henriques, Andreia Zerbib, Philipe Moyer, Mary Ann Chastre, Eric Jordan, Peter |
dc.subject.por.fl_str_mv |
Vias de Transdução de Sinal e Patologias Associadas Rac1b Cancro Colorectal Doença Inflamatória do Intestino NSAID Ibuoprofen |
topic |
Vias de Transdução de Sinal e Patologias Associadas Rac1b Cancro Colorectal Doença Inflamatória do Intestino NSAID Ibuoprofen |
description |
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. The analysis of colorectal tumors revealed that overexpression of splice variant Rac1b occurs in around 80% of tumors with mutant B-Raf and both events were shown to cooperate in tumor cell survival. Here we provide evidence for increased expression of Rac1b in samples from inflammatory bowel disease patients as well as following experimentally induced colitis in mice. The increase of Rac1b in the mouse model was specifically prevented by the non-steroidal anti-inflammatory drug ibuprofen, which also inhibited Rac1b expression in cultured HT29 colorectal tumour 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 and in cancer prophylaxis following colon inflammation disorders. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-02-08T14:33:13Z 2013-01 2013-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.18/1200 |
url |
http://hdl.handle.net/10400.18/1200 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Neoplasia. 2013 Jan;15(1):102-11 1522-8002 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Neoplasia Press |
publisher.none.fl_str_mv |
Neoplasia Press |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799132094502273024 |