@article{APS9662,
author = {Li-mei FANG and Bin LI and Jun-jie GUAN and Hai-dong XU and Gen-hai SHEN and Quan-gen GAO and Zheng-hong QIN},
title = {Transcription factor EB is involved in autophagymediated chemoresistance to doxorubicin in human cancer cells},
journal = {Acta Pharmacologica Sinica},
volume = {38},
number = {9},
year = {2017},
keywords = {},
abstract = {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.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/9662}
}