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. 2017 Apr 14;8(27):43602–43616. doi: 10.18632/oncotarget.17115

Figure 6. Dual bortezomib and K145 treatment induces synergistic ER stress.

Figure 6

A. LP-1 cells were cultured with vehicle and sub-cytotoxic concentrations of bortezomib (5 nM), K145 (7 μM) or both for 4 h and examined for levels of ER stress and UPR activation by Western blot. B. LP-1 cells were cultured with vehicle and sub-cytotoxic concentrations of bortezomib (3 nM), K145 (4 μM) or both for 16 h and examined for levels of ER stress and UPR activation by Western blot. Co-administration of bortezomib and K145 to LP-1 cells increases expression of spliced XBP1 mRNA and produces a marked increase in CHOP gene expression by RT-qPCR at 16 h shown as bar charts below the Western blots. Mean±SD of triplicate determinations are shown with expression levels relative to control cultures and normalised to GAPDH. C. LP-1 cells were cultured with the indicated concentrations of bortezomib and K145 for 16 h. Levels of IRE1α and stress kinase activation were assessed by Western blot. α-tubulin was used as a loading control. D. Proposed schematic of how bortezomib and K145 combine to induce synergistic ER stress and UPR activation that results in pro-apoptotic IRE1α signalling.