Transcription factor EB is involved in autophagy-mediated chemoresistance to doxorubicin in human cancer cells.
Acta Pharmacol Sin
; 38(9): 1305-1316, 2017 Sep.
Article
en En
| MEDLINE
| ID: mdl-28603284
Transcription factor EB (TFEB) is a master regulator of autophagy activity and lysosomal biogenesis, but its role in autophagy-mediated cell survival and chemotherapy resistance is not completely understood. In this study, we explored whether TFEB played an important role in autophagy-mediated chemotherapy resistance in human cancer LoVo and HeLa cells in vitro. Treatment of human colon cancer LoVo cells with doxorubicin (0.5 µmol/L) induced autophagy activation and nuclear translocation of TFEB, which resulted from inactivation of the mTOR pathway. In both LoVo and HeLa cells, overexpression of TFEB enhanced doxorubicin-induced autophagy activation and significantly decreased doxorubicin-induced cell death, whereas knockdown of TFEB with small interfering RNA blocked doxorubicin-induced autophagy and significantly enhanced the cytotoxicity of doxorubicin. In LoVo cells, autophagy inhibition by 3-methyladenine (3-MA) or knockdown of autophagy-related gene Atg5 increased cell death in response to doxorubicin, and abolished TFEB overexpression-induced chemotherapy resistance, suggesting that the inhibition of autophagy made cancer cells more sensitive to doxorubicin. The results demonstrate that TFEB-mediated autophagy activation decreases the sensitivity of cancer cells to doxorubicin.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autofagia
/
Doxorrubicina
/
Resistencia a Antineoplásicos
/
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice
/
Antibióticos Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Acta Pharmacol Sin
Asunto de la revista:
FARMACOLOGIA
Año:
2017
Tipo del documento:
Article
Pais de publicación:
Estados Unidos