Fig. 6

Mechanism for selinexor and doxorubicin synergy. a Parental MM cell lines 8226 and U226 and drug-resistant 8226B25, 8226Dox6, and U266PSR cells were treated with doxorubicin (2 μM), selinexor (300 nM), or the combination for 20 h. Both parental and drug-resistant cell lines, when treated with the combination of selinexor and doxorubicin, had significantly increased DNA damage as shown by increased phospho-H2AX (Ser139) expression (n = 4). b SiRNA knockdown of TOP2A resulted in a substantial decrease in DNA damage (phospho-H2AX (Ser139)) and apoptosis, suggesting that selinexor and doxorubicin induced DNA damage, and subsequent apoptosis is TOP2A dependent. Inset, TOP2A knockdown (Western blot)