Combination CC-5013 and rapamycin affects growth and survival signaling pathways in MM1.S cells. MM1.S cells were treated with CC-5013 (1 μM), rapamycin (1 nM), or combined therapy for up to 8 hours. (A) Down-regulation of the MAPK pathway by CC-5013 and the STAT pathway by rapamycin. Rapamycin does not affect or it up-regulates MAPK pathway, evidenced by the phosphorylation of pERK and pMEK1/2. Combined CC-5013 and rapamycin inhibits both pathways, demonstrated by the down-regulation of pERK, pMEK1/2, and pSTAT. These agents, alone and in combination, inhibit pP65NFκB. (B) Complete inhibition of p70S6 kinase phosphorylation by rapamycin alone or by combination therapy, whereas CC-5013 alone has no effect.