Fig. 4

Effect of the PI3K/Akt/mTOR and MAPK signaling pathways on CBL0137-induced apoptosis and autophagy. A Singal pathway enrichment analysis of CBL0137 2.0 μM treated and untreated groups by RNA-seq in SU-DHL-4, Raji, and Jeko-1 cells (P < 0.05). B B-NHL cells were incubated with CBL0137 (0.5–2.0 μM) for 24 h, after which levels of PI3K, AKT, mTOR, and their phosphorylated forms were determined by western blotting. C Western blotting was used to detect the expression changes of related downstream molecules in the MAPK signaling pathway after CBL0137 (0.5–2.0 μM) treatment, including ERK1/2, p38 MAPK, p-p38 MAPK, GSK3β, and their phosphorylated forms. D B-NHL cells were pretreated with 10 μM U0126 or 10 μM LY294002 for 2 h followed by exposed to 2.0 μM CBL0137 for 24 h, respectively. Western blotting was used to detect the expression of apoptotic and autophagic marker proteins, and GAPDH was used as an internal control. E The expression level of cleaved PARP and the conversion of LC3 were analyzed by western blotting when 10 μM U0126 and 10 μM LY294002 were used together. F B-NHL cells were treated with 2.0 μM CBL0137 from 0 to 24 h. Western blotting was used to analyze the expression of key molecules involved in apoptosis and autophagy, as well as changes in the phosphorylation status of PI3K, Akt, mTOR, and ERK1/2. G B-NHL cells were treated with CBL0137 or in combination with NAC. The expression of p-PI3K, p-AKT, p-mTOR, and p-ERK1/2 was detected by western blotting in B-NHL cells