Second-generation Src/Abl inhibitor bosutinib effectively induces apoptosis in human esophageal squamous cell carcinoma (ESCC) cells via inhibiting Src/Abl signaling.
Neoplasma
; 67(1): 54-60, 2020 Jan.
Article
em En
| MEDLINE
| ID: mdl-31777258
ABSTRACT
Esophageal cancer is a prevalent type of cancer worldwide and is ranked sixth among cancer-associated mortalities. Aberrant activation of the non-receptor tyrosine kinase Src and c-Abl contribute to the progression of ESCC. Thus, targeting these kinases to treat ESCC is a promising strategy. In this paper, we report that the potent dual Src/Abl inhibitor bosutinib exerts anti-tumor effects on ESCC. Bosutinib inhibits ESCC cell proliferation in a dose-dependent manner. Furthermore, bosutinib suppresses the colony formation ability of ESCC cells. Mechanistically, bosutinib effectively inhibits c-Abl and Src and its downstream signaling pathways, PI3K/AKT/mTOR and JAK/STAT3. In addition, bosutinib enhances the cytotoxic effects of doxorubicin on ESCC cells. In summary, our results reveal that Src and Abl are potential therapeutic targets in ESCC and that the novel Src/Abl inhibitor bosutinib alone or in combination with other chemotherapeutic agents may be a viable option for treating ESCC patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
/
Neoplasias Esofágicas
/
Transdução de Sinais
/
Apoptose
/
Carcinoma de Células Escamosas do Esôfago
/
Compostos de Anilina
/
Nitrilas
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article