The Study of Bortezomib Alone or in Combination with Arsenic Trioxide on Multidrug Resistance of HL60/ADR cells.

Proteĉ¢msome inhibitor bortezomib has used in treatment of hematology malignancies widely. We found it may reduce cell survival rate of HL60/ADR cell line and induce cell apoptosis in previous study. Now we are to investigate the effect of bortezomib alone or combined with arsenic trioxide (As₂O₃) on reversing multidrug resistance of HL60/ADR cell line and the possible machines.

HL60/ADR cells were incubated with bortezomib at different doses alone and in combination with As₂O₃. The proliferation ratio was observed by MTT assay. Cell apoptosis was studied by fluorescence microscopy and flow cytometry. Intracellular concentration of daunorubicin (DNR) and multidrug resistance related protein-1 (MRP₁) was determined by flow cytometry. P65Ap-p65Abcl-2AbaxAcaspase-3Acaspase-9APARP proteins were determined by western blot.

In bortezomib-treated tumor cells, inhibition rate increased in time- and dose-dependently, as well as apoptotic cells. Compared to bortezomib alone, combination with As₂O₃ inhibited the proliferation and induced the apoptosis of HL60/ADR cells more evident. Bortezomib can enhance the intraceflular accumulation of DNR and decrease MRP₁ in HL60/ADM cells. The dual combination of As₂O₃ with bortezomib presents a superior anticancer and MRP₁-decreased efficiency to either one of the drugs alone. Bortezomib can also elevate the expression of bax, caspase-3, caspase-9, PARP, and decelerate the expression of bcl-2, NF-κB p65, p-p65.

Bortezomib can reverse multidrug resistance of HL60/ADR cells and decrease the expression of MRP₁ in cells. When combined with As₂O_3, it appears to synergistic effects. Its mechanisms might be associated with the inhibition of NF-κB activation, also with inhibiting anti-apoptosis proteins, boosting pro-apoptosis proteins, with followed activating caspase pathway.

No relevant conflicts of interest to declare.