Figure 5.

Combined targeting of CDK9 and BRD4 results in the inhibition of proliferation and tumor growth. (A) In vivo anti-tumor efficacy of JQ1 and CDKI-73 as a single agent or in combination against A673-bearing Rag2^−/−γ_C^−/− mice xenografts. A673 cells were injected subcutaneously (s.c.) into mice. Once tumor was palpable mice were randomly allocated into four groups (7 mice/group) and treated with vehicle (DMSO), JQ1 (50 mg/kg, i.p., daily), CDKI-73 (50 mg/kg, p.o. every other day), or with CDKI-73 in combination with JQ1. For the combination study, JQ1 was given i.p. daily, followed by CDKI-73 every other day. Two-way ANOVA; *** p-value <0.0005. (B) As soon as tumors reached 1 cm³, mice were sacrificed and tumors were analyzed for cleaved caspase 3 by immunohistochemistry (see Materials and Methods). Representative results of A673 tumors are shown (4× original magnification). (C) The level of caspase 3 in A673 tumors. The percentage of cleaved caspase 3 positive cells in five fields per tumor is given; t-test, * p-value <0.05. (D) The percentage of Ki67 positive cells in five fields per tumor is given; t-test, * p-value <0.05.