Novel PI3K/Akt/mTOR signaling inhibitor, W922, prevents colorectal cancer growth via the regulation of autophagy.
Int J Oncol
; 58(1): 70-82, 2021 01.
Article
en En
| MEDLINE
| ID: mdl-33367926
ABSTRACT
W922, a novel PI3K/Akt/mTOR pathway inhibitor, exhibits efficient antitumor effects on HCT116, MCF7 and A549 human cancer cells compared with other synthesized compounds. The present study aimed to investigate its antitumor effects on colorectal cancer cells. A total, of seven different colorectal cell lines were selected to test the antiproliferation profile of W922, and HCT116 was found to be the most sensitive cell line to the drug treatment. W922 inhibited HCT116 cell viability and cell proliferation in vitro in concentration and timedependent manners. Furthermore, W922 suppressed the tumor growth in a xenograft mouse model and exhibited low toxicity. The proteomic alterations in W922treated HCT116 cells were found to be associated with cell cycle arrest, negative regulation of signal transduction and lysosomerelated processes. W922 caused cell cycle arrest of HCT116 cells in G0G1 phase, but only triggered slight apoptosis. In addition, the PI3K/Akt/mTOR signaling proteins were dephosphorylated upon W922 treatment. It has been reported that inhibition of mTOR is relevant to autophagy, and the present results also indicated that W922 was involved in autophagy induction. An autophagy inhibitor, chloroquine, was used to cotreat HCT116 cells with W922, and it was identified that the cell cycle arrest was impaired. Moreover, cotreatment of W922 and chloroquine led to a significant population of apoptotic cells, thus providing a promising therapeutic strategy for colorectal cancer.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
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Protocolos de Quimioterapia Combinada Antineoplásica
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Inhibidores de Proteínas Quinasas
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Int J Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2021
Tipo del documento:
Article