Exosomes promote cetuximab resistance via the PTEN/Akt pathway in colon cancer cells
Braz. j. med. biol. res
; 51(1): e6472, 2018. graf
Artigo
em Inglês
| LILACS
| ID: biblio-889011
Biblioteca responsável:
BR1.1
ABSTRACT
Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt. Furthermore, reduced PTEN and increased phosphorylated Akt levels were found in Caco-2 cells after exposure to RKO cell-derived exosomes. Moreover, an Akt inhibitor prevented RKO cell-derived exosome-induced drug resistance in Caco-2 cells. These findings provide novel evidence that exosomes derived from cetuximab-resistant cells could induce cetuximab resistance in cetuximab-sensitive cells, by downregulating PTEN and increasing phosphorylated Akt levels.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
LILACS
Assunto principal:
Neoplasias do Colo
/
PTEN Fosfo-Hidrolase
/
Proteínas Proto-Oncogênicas c-akt
/
Exossomos
/
Cetuximab
/
Antineoplásicos Imunológicos
Limite:
Humanos
Idioma:
Inglês
Revista:
Braz. j. med. biol. res
Assunto da revista:
Biologia
/
Medicina
Ano de publicação:
2018
Tipo de documento:
Artigo
País de afiliação:
China
Instituição/País de afiliação:
China Medical University/CN