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. 2011 Jun 23;2(6):e174. doi: 10.1038/cddis.2011.58

Figure 5.

Figure 5

ABT-737 sensitization of spheroids to bortezomib is dependent on Bim and aided by ablation of Mcl-1. (a) Bim was ablated in M28 and REN cells and, 24 h later, cells were plated to generate monolayers and spheroids, exposed to bortezomib 25 nM and/or ABT-737 1 μM for 24 h and lysed and probed for Bim at 72 h after siRNA (see immunoblot insert), the time when cells were counted for the presence of apoptosis. The absence of Bim in spheroids completely abolished the apoptotic effect of ABT-737 when given alone and significantly reduced the effect when given with bortezomib. (*P<0.05 compared with control siRNA, ++P<0.05 spheroids versus monolayers, n=3). (b) Mcl-1 was ablated, as performed for Bim above (see immunoblot insert). The absence of Mcl-1 reduced the acquired multicellular resistance of spheroids to bortezomib. The absence of Mcl-1 also increased the apoptotic response to ABT-737 when given alone or in combination with bortezomib. (*P<0.05 compared with control siRNA, ++P<0.05 spheroids versus monolayers, n=3)