Objective To investigate the effect of THZ1, a selective inhibitor of cyclin-dependent protein kinase 7(CDK7), on the proliferation and apoptosis of human breast cancer cell lines MCF7, SkBr3 and Hs578T.

Methods MTT, flow cytometry and Western blot were used in the experiment to detect cell viability, cell cycle and apoptosis.

Results After treated with 500 nmol/L THZ1, the number of cells was obviously decreased based on microscope observation. MTT assay showed that the proliferation of breast cancer cells was inhibited in a dose-and time-dependent manner after THZ1 treatment. Cells were synchronized at the G₁/S transition by starved for 24h, and then treated with indicated doses of THZ1 for 24h. FCM results showed that the number of cells in G₂/M phase was increased, indicating the G₂/M phase cell cycle arrest was induced. Furthermore, THZ1 induced cells apoptosis in a dose-and time-dependent manner. The expression of Cleaved-PARP were significantly up-regulated and anti-apoptotic gene Bcl-2 were down-regulated, and the NF-κB and GSK3β pathway were activated via increasing the phosphorylation of p65 and GSK3β.

Conclusion THZ1 can inhibit the proliferation of MCF7, SkBr3 and Hs578T cells, induce cell cycle arrest and cell apoptosis in a dose-and time-dependent manner. It suggested that THZ1 can be used as a potential candidate drug for breast cancer.