Fig. 4
Modification of combination therapy by pulsatile application of ABT-199. a BV173 (left) and SUPB15 (right) cells were treated for a total of 96 h with DAS (50 and 10 nM, respectively) and DEX (50 and 10 nM, respectively). ABT-199 (50 nM in BV173 and 10 nM in SUPB15, respectively) was added either in parallel (ABT-199 AUC = 1) or as sequential treatment for the last 24 h in either equal concentration (equivalent to ABT-199 AUC = 0.25) or 4-fold higher concentration (equivalent to ABT-199 AUC = 1). Values are expressed as means ± SD (n = 3). p-values were calculated by Student’s t-test. b NSG recipients received 1 × 106 BV173 cells intravenously. Treatment started 1 week after tumor inoculation. Kaplan–Meier survival curves of recipients treated with DEX (1 mg/kg) and DAS (10 mg/kg) by oral gavaging 5 days per week and pulsatile therapy with ABT-199 (constant dose of 20 mg/kg) on the 4th day (96 h) of the weekly treatment cycle are shown. Treatment was stopped after week 6. Log-rank test was used for statistical survival analyses (**p ≤ 0.01)
