Inhibition of cyclin-dependent kinase 7 suppresses human hepatocellular carcinoma by inducing apoptosis

Journal of Cellular Biochemistry
Liqiang ZhongKaijian Lei

Abstract

Increasing evidence has shown that THZ1, a covalent cyclin-dependent kinase 7 (CDK7) inhibitor, exhibits therapeutic effects in various tumors. However, the possible effect of THZ1 on hepatocellular carcinoma (HCC) remains unknown. Our study was to investigate the roles of THZ1 in HCC cells and in subcutaneous HCC model and illustrate the molecular mechanisms. The phosphorylation levels of Ser2, Ser5, and Ser7 within RNA polymerase II (RNAPII) C-terminal domain (CTD) and the expression levels of Ki67, Mcl-1, survivin, XIAP, and p53 in HCC cells under different conditions were examined by Western blot analysis. Cell growth and apoptosis were assessed via 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. Tumor volume was assessed in HCC mice with THZ1 or vehicle treatment and immunohistochemical (IHC) analysis was conducted on excised tumors. THZ1 significantly inhibited the phosphorylation of Ser2, Ser5, and Ser7 within RNAPII-CTD in the dose-dependent and irreversible manner. MTT assay and flow cytometry analysis showed that THZ1 inhibited HCC cell proliferation and induced apoptosis, respectively. Western blot analysis indicated THZ1 significantly upregulated p5...Continue Reading

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Citations

May 10, 2020·Cancer Metastasis Reviews·Georgina P SavaSimak Ali
Nov 14, 2020·Expert Opinion on Investigational Drugs·Hanzhi LiangHao Fang
Mar 10, 2020·Journal of Medicinal Chemistry·Sarah DiabShudong Wang
Sep 12, 2021·Nature Reviews. Molecular Cell Biology·Helen K MatthewsRobertus A M de Bruin

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