Fig. 4
From: Targeting enolase 1 reverses bortezomib resistance in multiple myeloma through YWHAZ/Parkin axis

Inhibitory effects of combination therapy with ENO1i and BTZ. A H929 and 8226 cells were cotreated with the indicated concentrations of ENOi (AP-III-a4, 0.2–1.6 µM) and various concentrations of BTZ (1–6 µM) either alone or in combination for 72 h. Cell viability was assessed using a CCK-8 assay. Dose-response matrix (inhibition) for ENOi and BTZ. The inhibition ratio is positively related to the degree of red. The drug interaction landscapes are based on the ZIP model. B Flow cytometry was used to detect the cell apoptosis of MM cells treated with ENO1i (AP-III-a4) and BTZ. C The viability of cells from MM patients were evaluated after ENO1i (AP-III-a4), BTZ, and combination treatment for 72 h. Pt# represents patient number. Pt#1 and Pt#4 were diagnosed with relapsed/refractory multiple myeloma (RRMM). Data are presented as the means ± SD of three independent experiments. D The medication process is shown above via a schematic diagram of passage. MM subcutaneous tumor-bearing mice were treated with either ENO1i (10 mg/kg), BTZ (1 mg/kg) or a combination of both. Normal saline was used as a control. Representative images of the tumours from each group (n = 5 mice/group). E Tumour sizes were measured every 2 days. Tumour volumes are displayed through the growth curve. F Tumour weights were detected in different treatment groups. G Averages and SDs of mice weights versus the time (mean weight SD). H Ki-67, TUNEL staining of the vehicle, ENO1i (AP-III-a4), BTZ, and combination treated xenograft tumour tissues (original magnification: ×400). *P < 0.05, **P < 0.01 and ***P < 0.001 versus the control group