Figure 7. DZNep kills CD138⁺ MM cells and co-operates in vitro and in vivo with bortezomib.

(a) Stromal HS-5 cells were seeded in 96-well plates at the density of 10⁴ cells/well and cultured for three days. Vehicle or DZNep (1 µM) was further added in five wells per culture condition and plates incubated for 24 and 48 h. Cell viability was determined by a MTS assay. On the graph are the means and SD values. ns, not significant. (b) Exponentially growing 8226 cells were separated into CD138^low and CD138^high populations. The sensitivity of CD138^high population and global population to DZNep (1 µM for 72 h) was compared by the MTS assay as before. ns, not significant with the Student’s t-test. (c) LP1 DZNep-resistant cells and JJN3 -sensitive cells were either treated with vehicle or DZNep 1 µM or bortezomib (Bort) 10–25 nM for 24 h or sequentially first with Bort then DZnep for 48 h. Cell proliferation was estimated by the MTS assay. Control samples referred to 100%. Here is shown a representative example from three independent experiments; each culture condition being in triplicate. Histograms show means ± SD, *p<0.05.