Wogonin derivative V8 enhances bortezomib efficacy in gastric carcinoma by disrupting lysosome-mediated drug resistance

Figure 4 V8 synergizes with bortezomib to inhibit gastric cancer cell growth. A: Cell viability assay was performed in different gastric cancer cells treated with V8 and bortezomib (BTZ) for 24 hours; B: Combination index was calculated in different gastric cancer cells; C and D: MGC-803 cells were treated with V8 (9 μM) and BTZ (100 nM) for 24 hours. Western blotting was carried out for analysis of indicated protein expression with β-actin as loading control; E and F: Cells were treated with V8 (9 μM), BTZ (100 nM), or benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethylketone (20 μM) for 24 hours, followed by flow cytometry assay for apoptosis analysis. Representative images (E) and quantitative data (F) are shown. ^bP < 0.01. ^dP < 0.0001. CI: Combination index; Bip: Immunoglobulin heavy chain binding protein; p-eIF2α: Phosphorylated eukaryotic translation initiation factor 2 alpha; Clpp: Caseinolytic mitochondrial matrix peptidase proteolytic subunit; DMSO: Dimethyl sulfoxide; BTZ: Bortezomib; V-FITC: Annexin V-fluorescein isothiocyanate; PI: Propidium iodide; Z-VAD-FMK: Benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethylketone.