Cyp1a1 is involved in drug resistance to bortezomib in CD138^- myeloma cells

One of the greatest challenges in multiple myeloma (MM) treatment is to overcome drug resistance. CD138^- MM cells show a more resistant phenotype to drugs than CD138⁺ cells. In this study, we demonstrated thatCD138^- cells are more resistant to bortezomib than CD138⁺ cells, mainly due to the higher cyp1a1 activity in CD138^- cells. Suppressing cyp1a1 activity in CD138^- cells by Notch inhibition, NF (cyp1a1 inhibitor) or cyp1a1 siRNA results in increased sensitivity of CD138^- cells to bortezomib treatment. Up-regulation of cpy1a1 activity in CD138⁺ cells by Dll1 simulation induced drug resistance to bortezomib. Our data showed that cyp1a1 activity is involved in drug resistance to bortezomib in CD138^- MM cells. It provided a new strategy of suppressing cyp1a1 activity to overcome drug resistance to bortezomib in clinical treatment.