A novel ribociclib derivative WXJ-103 exerts anti-breast cancer effect through CDK4/6.

Abstract

The triple-negative breast cancer (TNBC) subtype is the most aggressive type of breast cancer with a low survival prognosis and high recurrence rate. There is currently no effective treatment to improve it. In this work, we explored the effect of a synthetic compound named WXJ-103 on several aspects of TNBC biology. The human breast cancer cell lines MDA-MB-231 and MCF-7 were used in the experiments, and the cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, and the cell migration and invasion abilities were detected by wound healing assay and Transwell invasion assay. Cell cycle and apoptosis experiments were analyzed by flow cytometry, and protein levels related to cyclin-dependent kinase (CDK) 4/6-cyclin D-Rb-E2F pathway were analyzed by western blotting. Then, in-vivo experiments were performed to determine the clinical significance and functional role of WXJ-103. The results show that WXJ-103 can inhibit the adhesion, proliferation, migration, and invasion of TNBC cells, and can arrest the cell cycle in G1 phase. The levels of CDK4/6-cyclin D-Rb-E2F pathway-related proteins such as CDK6 and pRb decreased in a dose-dependent manner. Therefore, the antitumor activity of WXJ-103 may depend on the inhibition of CDK4/6-cyclin D1-Rb-E2F pathway. This research shows that WXJ-103 may be a new promising antitumor drug, which can play an antitumor effect on TNBC and provide new ideas for the treatment of TNBC.