Abstract:
Objective To evaluate the schedule-dependent effect of bortezomib (BTZ) combined with fludarabine (FLU) on the cell proliferation and apoptosis of the HUT-78 cell line.
Methods The half-maximal inhibitory concentration (IC50) of BTZ and FLU was estimated by 3-(4, 5-deimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide. Flow cytometry was used to analyze the effects of BTZ or FLU alone on the cell cycle, as well as the rate of apoptosis when they were combined in different sequences. The protein level of cleaved caspase-3 in HUT-78 cells was determined by Western blot.
Results The IC50 of BTZ or FLU alone for HUT-78 cell were 53.84 nmol/L ± 9.31 nmol/L and 2.54 mmol/L ± 0.33 mmol/L, respectively, at 24 h. BTZ promoted cell cycle arrest at the S phase, whereas FLU blocked cells at the G0–G1 phase. In cell apoptosis, the rate of the BTZ→FLU group was higher than those of other groups (P < 0.01). Western blot showed that compared with the concurrent group and the FLU→BTZ group, the protein level of cleaved caspase-3 was highest in the BTZ→FLU group (P < 0.01).
Conclusion BTZ combined with FLU, especially BTZ followed by FLU, induces a higher apoptosis rate in the HUT-78 cell line. This sequential usage of BTZ and FLU is available as a clinical therapy.