Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 21296-21303 |
| Number of pages | 8 |
| Journal | International Journal of Clinical and Experimental Medicine |
| Volume | 9 |
| Issue number | 11 |
| State | Published - Dec 2016 |
Keywords
- Bortezomib
- CD138
- Cyp1a1
- Drug resistance
- Myeloma