Figure 6: Doxorubicin or dinaciclib cooperates with ABT-199 to kill SCLC cells.
From: Targeting the differential addiction to anti-apoptotic BCL-2 family for cancer therapy
(a) H196 cells, treated with dinaciclib or doxorubicin for 18 h, were assessed by immunoblot analysis. (b) A summary of EC50s of ABT-199. Cell death response to 1 μM ABT-199 was quantified by annexin-V staining at 48 h (mean±s.d., n=3). (c) The indicated cell lines, treated with 2 μM doxorubicin±1 or 2 μM ABT-199, were quantified by annexin-V staining at 24 h for H2171 and H446 or at 48 h for H196 and SW1271 (mean±s.d., n=3). (d) The indicated cell lines, treated with 10–20 nM dinaciclib±1 or 2 μM ABT-199, were quantified by annexin-V staining at 24 h for H2171 and H446, at 48 h for H196, or at 72 h for SW1271 (mean±s.d., n=3). *P<0.05, **P<0.01 and ***P<0.001 (Student’s t-test). (e) NSG mice bearing H446 xenografts were treated with vehicle (n=6), ABT-199 (100 mg kg−1, n=8), doxorubicin (2 mg kg−1, n=8), or combined ABT-199 and doxorubicin (n=8). tumour volumes were measured twice weekly by caliper (mean±s.d.). *P=0.0022 and **P<0.0001 (two-way analysis of variance (ANOVA)). (f) NSG mice bearing H446 xenografts were treated with vehicle (n=8), ABT-199 (100 mg kg−1, n=8), dinaciclib (20 mg kg−1, n=8), or combined ABT-199 and dinaciclib (n=8). *P=0.0002; **P=0.0034 (two-way ANOVA). (g) NSG mice bearing patient-derived SCLC xenografts were treated with vehicle (n=5), ABT-199 (100 mg kg−1, n=4), doxorubicin (2 mg kg−1, n=6), or combined ABT-199 and doxorubicin (n=4). *P=0.0029; **P<0.0001 (two-way ANOVA). (h) NSG mice bearing patient-derived SCLC xenografts were treated with vehicle (n=6), ABT-199 (100 mg kg−1, n=6), dinaciclib (30 mg kg−1, n=6), or combined ABT-199 and dinaciclib (n=8). **P<0.0001 (two-way ANOVA). Unprocessed original scans of blots are shown in Supplementary Fig. 11.
