Fig. 7

The interconnected molecular events in resistant MCL cells upon BTZ treatment. a In BTZ-resistant MCL cells, BTZ-induced ROS enhances PI3K-AKT signaling and cytoprotective autophagy. Activation of PI3K-AKT pathway blocks nuclear translocation of BACH2, thus removing the transcriptional repression of BACH2 on HMOX1. Increased HO-1 further maintains ROS in a relative lower tumor-promoting level and induces autophagy formation, leading to cell survival. b 3-MA increases BTZ-induced cytotoxicity via dual inhibition of PI3K-AKT pathway and autophagy formation. Particular attention should be paid to the antioxidants supplements which aggravate BTZ resistance by stabilizing BACH1