American Society of Hematology

Figure 7

$Figure 7. Synergistic interaction between GX15-070 and bortezomib in MCL primary cells. (A) Primary cells from 4 representative patients with MCL were treated with 5 or 10 nM bortezomib and increasing doses of GX15-070 (0.1-1 μM) for 18 hours. Cytotoxicity was evaluated by cytofluorimetric analysis of Annexin V–APC. Linked arrows in patients no. 4 and no. 7 indicate equivalent cytotoxicities. Single arrows in patients no. 2 and no. 9 indicate the sensitizing effect of GX15-070 in these bortezomib-resistant patients. Results represent the mean ± SD of 3 independent experiments (B) Mcl-1, Bak, and Noxa expressions were analyzed by Western blot in 50 μg of total protein extracts from cells of patient no. 2 cotreated with 1 μM GX15-070 and/or 5 nM bortezomib for 18 hours. α-tubulin was also probed as an equal loading control. (C) Cells from patient no. 2 were treated with 1 μM GX15-070 and/or 5 nM bortezomib for 5 hours. Mcl-1, Bak, and Noxa proteins were analyzed in Mcl-1–immunoprecipitated and nonimmunoprecipitated fractions as described in “Patients, materials, and methods.” Western blot images are representative results from 3 independent experiments.$

Synergistic interaction between GX15-070 and bortezomib in MCL primary cells. (A) Primary cells from 4 representative patients with MCL were treated with 5 or 10 nM bortezomib and increasing doses of GX15-070 (0.1-1 μM) for 18 hours. Cytotoxicity was evaluated by cytofluorimetric analysis of Annexin V–APC. Linked arrows in patients no. 4 and no. 7 indicate equivalent cytotoxicities. Single arrows in patients no. 2 and no. 9 indicate the sensitizing effect of GX15-070 in these bortezomib-resistant patients. Results represent the mean ± SD of 3 independent experiments (B) Mcl-1, Bak, and Noxa expressions were analyzed by Western blot in 50 μg of total protein extracts from cells of patient no. 2 cotreated with 1 μM GX15-070 and/or 5 nM bortezomib for 18 hours. α-tubulin was also probed as an equal loading control. (C) Cells from patient no. 2 were treated with 1 μM GX15-070 and/or 5 nM bortezomib for 5 hours. Mcl-1, Bak, and Noxa proteins were analyzed in Mcl-1–immunoprecipitated and nonimmunoprecipitated fractions as described in “Patients, materials, and methods.” Western blot images are representative results from 3 independent experiments.

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