Figure 4
Figure 4. Ectopic aurora A expression inhibits antimyeloma effect of aurora inhibitors. OPM-2 cells were transfected with aurora A (Aur A) or empty vector (EV); cells were selected in vitro and then synchronized by double thymidine block. Four hours after release of the block, lysates were immunoblotted for aurora A expression as well as total histone 3B and phosphorylated histone (on serine 10) as shown in panel A. (B-C) Isogenic transfected cells were treated with increasing concentrations of either ZK (B) or VX-680 (C) and similarly synchronized and immunoblotted for total histone or phosphorylated histone. (D) Aurora A–transfected cells (▪) or empty vector control cells (EV, □) were exposed to increasing concentrations of VX-680, ZK, or bortezomib (PS-341) for 48 hours, after which percent inhibition of growth was determined in MTT assays. Results are means of 3 experiments. The percent inhibition induced by VX-680 and ZK was significantly less (P < .05) in aurora A–transfected cells treated with 25, 50, and 200 nM VX-680 and 500 and 1000 nM ZK.

Ectopic aurora A expression inhibits antimyeloma effect of aurora inhibitors. OPM-2 cells were transfected with aurora A (Aur A) or empty vector (EV); cells were selected in vitro and then synchronized by double thymidine block. Four hours after release of the block, lysates were immunoblotted for aurora A expression as well as total histone 3B and phosphorylated histone (on serine 10) as shown in panel A. (B-C) Isogenic transfected cells were treated with increasing concentrations of either ZK (B) or VX-680 (C) and similarly synchronized and immunoblotted for total histone or phosphorylated histone. (D) Aurora A–transfected cells (▪) or empty vector control cells (EV, □) were exposed to increasing concentrations of VX-680, ZK, or bortezomib (PS-341) for 48 hours, after which percent inhibition of growth was determined in MTT assays. Results are means of 3 experiments. The percent inhibition induced by VX-680 and ZK was significantly less (P < .05) in aurora A–transfected cells treated with 25, 50, and 200 nM VX-680 and 500 and 1000 nM ZK.

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