Liver fibrosis is a common pathological process of all chronic
liver diseases. Hepatic stellate cells (HSCs) play a central role in the development of
liver fibrosis.
Cyclin-dependent kinase 9 (CDK9) is a cell cycle
kinase that regulates
mRNA transcription and elongation. A CDK9 inhibitor
SNS-032 has been reported to have good effects in anti-
tumor. However, the role of
SNS-032 in the development of
liver fibrosis is unclear. In this study,
SNS-032 was found to alleviate hepatic
fibrosis by inhibiting the activation and inducing the apoptosis of active HSCs in
carbon tetrachloride-induced model mice. In vitro,
SNS-032 inhibited the activation and proliferation of active HSCs and induced the apoptosis of active HSCs by downregulating the expression of CDK9 and its downstream signal transductors, such phosphorylated
RNA polymerase II and Bcl-2. CDK9
short hairpin RNA was transfected into active HSCs to further elucidate the mechanism of the above effects. Similar results were observed in active HSCs after CDK9 knockdown. In active HSCs with CDK9 knockdown, the expression levels of CDK9, phosphorylated
RNA polymerase II, XIAP, Bcl-2, Mcl-1, and ɑ-SMA significantly decreased, whereas those of cleaved-PARP1 and Bax decreased prominently. These results indicated that
SNS-032 is a potential drug and CDK9 might be a new prospective target for the treatment of
liver fibrosis.