TY - JOUR AU - FANG Li-mei AU - LI Bin AU - GUAN Jun-jie AU - XU Hai-dong AU - SHEN Gen-hai AU - GAO Quan-gen AU - QIN Zheng-hong PY - 2017 TI - Transcription factor EB is involved in autophagymediated chemoresistance to doxorubicin in human cancer cells JF - Acta Pharmacologica Sinica; Vol 38, No 9 (September 2017): Acta Pharmacologica Sinica Y2 - 2017 KW - N2 - 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. UR - http://www.chinaphar.com/article/view/9662