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A novel ribociclib derivative WXJ-103 exerts anti-breast cancer effect through CDK4/6
Jing Ji1, Zhen Zhang1, Xingbei He1
1Department of Pharmacology, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang.
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.
Insights
WXJ-103, a novel compound, effectively inhibits triple-negative breast cancer (TNBC) cell growth, migration, and invasion. It also arrests the cell cycle and impacts key proteins, showing promise as a new TNBC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis and limited treatment options.
- Developing novel therapeutic strategies for TNBC remains a critical unmet need in cancer research.
Purpose of the Study:
- To investigate the anti-tumor effects of the synthetic compound WXJ-103 on triple-negative breast cancer (TNBC) cells.
- To elucidate the underlying molecular mechanisms of WXJ-103's action, particularly its impact on cell cycle and key signaling pathways.
Main Methods:
- Utilized human breast cancer cell lines (MDA-MB-231, MCF-7) for in vitro studies.
- Assessed cell viability (MTT assay), migration (wound healing assay), invasion (Transwell assay), cell cycle, and apoptosis (flow cytometry).
- Analyzed protein expression related to the CDK4/6-cyclin D-Rb-E2F pathway via Western blotting and conducted in vivo experiments.
Main Results:
- WXJ-103 significantly inhibited TNBC cell adhesion, proliferation, migration, and invasion.
- The compound induced G1 phase cell cycle arrest and modulated the expression of proteins within the CDK4/6-cyclin D1-Rb-E2F pathway, including decreased levels of CDK6 and pRb.
- In vivo studies confirmed the clinical significance and functional role of WXJ-103 in suppressing tumor growth.
Conclusions:
- WXJ-103 exhibits potent anti-tumor activity against TNBC, potentially through the inhibition of the CDK4/6-cyclin D1-Rb-E2F pathway.
- WXJ-103 represents a promising novel therapeutic agent for TNBC, offering new avenues for treatment development.
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