Figure 7.

ADAM10 inhibitors reduce Hodgkin lymphoma cell growth and ATP content and enhance brentuximab- vedotin effect. (A) L428 (left) or L540 (right) cells (10⁴) were added to LN-MSC16412 (10³) previously seeded into 96 microwell plates in the presence of brentuximab-vedotin (BtxVed) (10 mg/mL), alone or in combination with 10 mM LT4 or MN8. After 96 hours (h), 200 ml cell suspension were collected and cells counted at the MACS Quant Analyzer 10 (Miltenyi Biotech GmbH). Results are shown as percentage of cell growth inhibition calculated as the number of cells/well in cultures with the indicated drugs referred to cultures in the solvent (dimethyl sufoxide [DMSO] 1:1,000), as described in the Online Supplementary Appendix. Mean ± standard deviation (SD) of quadruplicates from three independent experiments. *P<0.01 and **P<0.001 vs. BtxVed or LT4 or MN8 alone. (B) Cultures were performed as in (A), with BtxVed used at 10 mg/mL and 1 mg/mL. After 96 h, ATP content measured by specific assay. Results are expressed as percent inhibition of luminescence in cultures exposed to the indicated drugs referred to cultures in the solvent (DMSO 1:1000), as described in the Online Supplementary Appendix. Mean ± SD of quadruplicates from three independent experiments.*P<0.001 vs. BtxVed or LT4 or MN8 alone **P<0.0001 vs. BtxVed alone.