Potent Activity of Composite Cyclin Dependent Kinase Inhibition against Hepatocellular Carcinoma.

ABSTRACT: Alterations in cell cycle regulators are common in hepatocellular carcinoma (HCC). We tested the efficacy of composite inhibition of CDKs 1, 2, 5, and 9 through dinaciclib on HCC. In vitro, dinaciclib exhibited potent antiproliferative activities in HCC cell lines regardless of Rb or c-myc expression levels. Dinaciclib significantly downregulated the phosphorylation of Rb (target of CDKs 1 and 2), ataxia telangiectasia mutated kinase (target of CDK5), and RNA polymerase II (target of CDK9) in the HCC cells. In xenograft studies, mice receiving dinaciclib tolerated the treatment well without significant body weight changes and exhibited a significantly slower tumor growth rate than the mice receiving vehicles. RNA interference (RNAi) of CDKs 1 and 9 was more effective in inhibiting the cell

SUBMITTER: Shao YY 

PROVIDER: S-EPMC6827105 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature