期刊
ACTA POLONIAE PHARMACEUTICA
卷 79, 期 3, 页码 353-365出版社
POLSKIE TOWARZYSTWO FARMACEUTYCZNE
DOI: 10.32383/appdr/152215
关键词
CDK4/6 inhibitors; breast cancer; anti-tumor activity; cell cycle; apoptosis
资金
- National Natural Science Foundation of China [82104174]
- Natural Science Foundation of Jiangsu Higher Education Institutions of China [20KJB350008]
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening [HY201703]
- Jiangsu Ocean University [KQ20014]
- Lianyungang Key Laboratory of Marine Biomedicine and Products [5507018035]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [SJCX22_1649, SJCX22_1650]
- Lianyungang Key Laboratory of Seafood Inspection Technology Research [5507018036]
Cyclin-dependent kinases (CDKs) play a crucial role in cell cycle regulation. Inhibiting the CDK4/6 pathway with the novel CDK4/6 inhibitor WXJ-111 showed significant anti-proliferative, anti-migratory, and anti-invasive effects on breast cancer cells, as well as downregulation of cell cycle factors and upregulation of apoptotic factors. WXJ-111 may be a promising candidate for breast cancer treatment.
Cyclin-dependent kinase (CDKs) are crucial drivers of cell cycle regulation. Aberrations in the CDK-Cyclin-Rb (cyclin-dependent kinase-retinoblastoma protein) pathway are common in cancer (over 90%). A promising therapeutic strategy against cancer involves regulating the CDK4/6-RB pathway. In this research, N1-(5-Fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo [d]imidazol-6-yl)pyrimidin-2-yl)-4-methyl-N3-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (WXJ-111) as a novel CDK4/6 inhibitor, inhibited the growth activity of MDA-MB-231, MCF-7, A498 and Hela cancer cell lines with IC50 values ranging from 10.88 +/- 1.24 to 65.87 +/- 6.74 mu M, showed significant anti-proliferation, anti-migration and anti-invasion effects on triple-negative breast cancer cells MDA-MB-231. Cell cycle factors such as CDK6, p-Rb, and E2F1 were significantly downregulated. Apoptotic factor Caspase-3 was upregulated, and anti-apoptotic factor Bcl-2 was downregulated. Compound WXJ-111 inhibited MDA-MB-231 cells based on evidence that cell cycle arrest and apoptosis are induced. In summary, the novel CDK4/6 inhibitor compound WXJ-111 may be a promising candidate drug for breast cancer treatment.
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