Blockage of AMPK-ULK1 pathway mediated autophagy promotes cell apoptosis to increase doxorubicin sensitivity in breast cancer (BC) cells: an in vitro study

Abstract Background Activation of autophagy flux contributed to resistance breast cancer (BC) cells current chemotherapeutic drugs, which seriously limited their therapeutic efficacy and facilitated BC recurrence in clinic. However, the detailed mechanisms are still not fully understood. In present study, we identified that inactivation AMPK-ULK1 signaling cascade mediated protective sensitized doxorubicin vitro. Methods Cell counting kit-8 (CCK-8) assay colony formation were performed evaluate cell proliferation abilities. Trypan blue staining was used examine viability, Annexin V-FITC/PI double method conducted determine apoptosis. The autophagosomes observed photographed by electronic microscope (EM). Western Blot analysis employed genes expressions at protein levels. Results parental doxorubicin-sensitive (DS-BC) exposed increasing concentrations establish doxorubicin-resistant (DR-BC) cells, DR-BC much more resistant high-dose treatment compared DS-BC cells. Interestingly, specifically increased LC3B-II/I ratio, promoted decreased p62 expression levels facilitate instead inhibitor 3-methyladenine (3-MA) enhanced cytotoxic effects on addition, proved triggered activating pathway. Functionally, phosphorylated AMPK (p-AMPK) ULK1 (p-ULK1) activate pathway inhibitors for (compound C) (SBI-0206965) blocked promote death slow down growth treated with doxorubicin. Conclusions Collectively, our vitro data indicated blockage might be a promising strategy increase sensitivity treatment.