Bortezomib-adapted cell lines have higher proteasome activity and tolerate lower chymotrypsin-like proteasome activity than PT cells. (A) Dose response to bortezomib (Bzm) in PT and BR cell lines. Viability by MTT assay at 48 hours normalized to the carrier control is shown. (B) Reversibility of bortezomib resistance in BR cell lines cultured in the absence of bortezomib. IC50 values were determined as shown in panel A at the indicated time points after bortezomib washout. (C) Baseline proteasome activity in PT and BR cell lines. Chymotrypsin activity was measured at 3 different time points over a 1-month period and data are normalized to the average activity in the corresponding PT cell line. Comparison was by Student t test: *P < .05; **P < .01. Trypsin and caspase-like activities were measured in duplicate and are shown for comparison. (D) Correlation between cell viability by MTT assay and chymotrypsin-like proteasome activity (arbitrary units) in PT and BR cell lines treated with increasing concentrations of bortezomib for 48 hours.
