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. 2018 Nov 5;128(12):5479–5488. doi: 10.1172/JCI120156

Figure 3. AZD9150 specifically inhibits STAT3 and decreases viability and induces apoptosis in leukemic cell lines.

Figure 3

(A) To demonstrate specific inhibition of STAT3-mediated gene expression, we treated the CMK cell lines transfected with STAT3- and STAT5-binding luciferase constructs with AZD9150 (2.5 μM) and control. A decrease in STAT3-mediated luciferase expression was observed, while no change in STAT5-mediated gene expression was seen. (B) qPCR of 4 leukemic cell lines transfected with AZD9150 (10 μM) showed a decreased expression of STAT3. (C) Multiple leukemic cells lines were transfected with AZD9150 (10 μM) and inactive structural analog control (10 μM). AZD9150 resulted in a significant decrease in viable cells. (D) Representative flow cytometry plots show increased apoptosis with AZD9150 treatment (5 μM) compared with the control oligonucleotide (5 μM). (E–G) Increased apoptosis was seen in multiple leukemic cell lines after AZD9150 transfection as compared with controls. (H) NOD-SCID mice were injected with CMK cells transfected with AZD9150 (10 μM) and the control oligonucleotide (10 μM). The 2 cohorts were followed over time for survival, and it was noted that the drug-treated mice had an improved median survival of 64 days compared with 43 days for the control oligonucleotide (P = 0.028). *P ≤ 0.05, **P ≤ 0.005.