Fig. 5.

Pharmacological inhibition of CDK9 reduces tumor burden and prolongs survival in HCC mouse model. (A) Diagram depicting generation of autochthonous HCC model in wild-type mice using hydrodynamic injection to deliver transposons expressing oncogene MYC to the liver together with CRISPR plasmid DNA expressing Cas9 and an sgRNA that directly targets p53 or Axin1 (ONC, oncogene; TSG, tumor suppressor gene). (B and C) Representative RNA Pol II pSer2 IHC staining images and quantification of pSer2 expression in liver tumors with NVP-2 treatment. (Scale bars, 50 μm.) (D) Representative ultrasound images of liver and tumor of mice upon NVP-2 or vehicle treatment for 3 wk. Red dotted lines indicate the tumor regions. White dotted lines indicate tumor degradation regions. (E) Representative H&E staining images of liver and tumor regions of mice treated with vehicle or NVP-2 for 2 wk. (F) Kaplan–Meier survival curves of mice treated with NVP-2 (2.5 mg/kg and 5 mg/kg) and vehicle. Results are demonstrated by indicated number of biological replicates in each group of mice in the graph. Statistical significance was calculated by Mantel–Cox test (**P < 0.01; ***P < 0.001). (G–I) Serological analysis of the concentrations of ALT, AST, and ALB in HCC-bearing mice on vehicle or NVP-2 (5 mg/kg) treatment for 3 wk. Results are demonstrated by four biological replicates in each group of mice. Statistical significance was calculated by two-tailed Student’s t test. Error bars correspond to mean ± SEM (*P < 0.05; n.s., not significant).