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

Figure 2 Lysosome affects the anticancer effect of bortezomib. A: Intracellular drug concentration was examined using liquid chromatography/mass spectrometry after cells were treated with bortezomib (BTZ) (100 nM) and bafilomycin A1 (100 nM) alone or in combination for 6 hours; B and C: MGC-803 cells were treated with indicated concentration of BTZ and L-leucyl-L-leucine methyl ester hydrochloride (1 mmol/L) for 6 hours, followed by staining of LysoSensor Green DND-189. Representative images (B) and quantification data (C) of flow cytometry were shown; D and E: Representative images (D) and quantified results (E) of immunofluorescent analysis for LAMP1 expression in different gastric cancer cell lines (scale bar: 10 μm); F: Cell viability assay was performed in different gastric cancer cells treated with BTZ; G: Spearman correlation was determined between half-maximal inhibitory concentration value for BTZ and cellular LAMP1 expression. ^bP < 0.01. ^cP < 0.001. ^dP < 0.0001. BTZ: Bortezomib; Baf-A1: Bafilomycin A1; LLOMe: L-leucyl-L-leucine methyl ester hydrochloride; DMSO: Dimethyl sulfoxide; MFI: Mean fluorescence intensity; DAPI: 4’,6-Diamidino-2-phenylindole; NS: No significance; IC₅₀: Half-maximal inhibitory concentration.