Figure 4
Figure 4. AZD1152-HQPA potentiates effect of conventional chemotherapeutic agents. PALL-2 (A,B) or MOLM13 (C-F) cells were cultured with AZD1152-HQPA (1-10 nM) and/or either vincristine (VCR, 0.1-1 μM) or daunorubicin (DNR, 3-30 nM). After 2 days, cell proliferation was measured by 3H-thymidine uptake. The percent inhibition was graphed (A,C,E) and the concentration of each compound that induced 50%, 75%, or 90% growth inhibition (IC25, IC50, IC75) was determined (data not shown). The combination index (CI) of AZD1152-HQPA and VCR (B,D), or AZD1152-HQPA and daunorubicin (F) at various dose effects (IC25, IC50, IC75) was calculated using the median effect method. CI values less than 1 indicate synergy; CI of 1 indicates an additive effect; and CI greater than 1 demonstrates antagonism between the 2 agents. Western blot analysis of activated caspase (cleaved PARP) in PALL-2 (G) or MOLM13 (H-I). PALL-2 (G) or MOLM13 (H) cells were cultured with AZD1152-HQPA (1-10 nM) and/or VCR (0.1-1 μM). MOLM13 (I) cells were cultured with AZD1152-HQPA (1-10 nM) and/or DNR (3-30 nM). After 12 hours, cells were harvested, and proteins were extracted and subjected to Western blot analysis. The membranes were sequentially probed with anti-PARP and anti–α-tubulin antibodies. Results represent 1 of the 3 experiments performed independently. AZD indicates AZD1152-HQPA; VCR, vincristine; and DNR, daunorubicin. Error bars represent SD.

AZD1152-HQPA potentiates effect of conventional chemotherapeutic agents. PALL-2 (A,B) or MOLM13 (C-F) cells were cultured with AZD1152-HQPA (1-10 nM) and/or either vincristine (VCR, 0.1-1 μM) or daunorubicin (DNR, 3-30 nM). After 2 days, cell proliferation was measured by 3H-thymidine uptake. The percent inhibition was graphed (A,C,E) and the concentration of each compound that induced 50%, 75%, or 90% growth inhibition (IC25, IC50, IC75) was determined (data not shown). The combination index (CI) of AZD1152-HQPA and VCR (B,D), or AZD1152-HQPA and daunorubicin (F) at various dose effects (IC25, IC50, IC75) was calculated using the median effect method. CI values less than 1 indicate synergy; CI of 1 indicates an additive effect; and CI greater than 1 demonstrates antagonism between the 2 agents. Western blot analysis of activated caspase (cleaved PARP) in PALL-2 (G) or MOLM13 (H-I). PALL-2 (G) or MOLM13 (H) cells were cultured with AZD1152-HQPA (1-10 nM) and/or VCR (0.1-1 μM). MOLM13 (I) cells were cultured with AZD1152-HQPA (1-10 nM) and/or DNR (3-30 nM). After 12 hours, cells were harvested, and proteins were extracted and subjected to Western blot analysis. The membranes were sequentially probed with anti-PARP and anti–α-tubulin antibodies. Results represent 1 of the 3 experiments performed independently. AZD indicates AZD1152-HQPA; VCR, vincristine; and DNR, daunorubicin. Error bars represent SD.

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