Inhibition of FOXO1-Mediated Autophagy Promotes Paclitaxel-Induced Apoptosis in MDA-MB-231 Cell Lines
Abstract Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancers and often produces resistance to paclitaxel (PTX) therapy. Autophagy plays an important cytoprotective role in PTX-induced tumor cell death and targeting autophagy is promising to improve the efficacy of tumor chemotherapy in recent years. Here, we reported that PTX induced both apoptosis and autophagy of MDA-MB-231 cells, and inhibition of autophagy enable to promote apoptotic cell death. Furthermore, we found that FOXO1 enhanced PTX-induced autophagy by a transcriptional activation pattern in MDA-MB-231 cells, which was associated with its downstream target genes ATG5, VPS34, BECN1 and MAP1LC3B. The knockdown of FOXO1 attenuated the survival of MDA-MB-231 cells under the PTX treatment. These findings will be beneficial to improve the treatment efficacy of PTX and to develop the autophagic target therapy of TNBC.