β-elemene induced apoptosis and senescence of triple-negative breast cancer cells through IGF1/IGF1R pathway.

Purpose: β-elemene has a wide range of anticancer effects and can be used in a variety of cancer types. This study mainly explored its mechanism of action on TNBC cells and provided theoretical basis for the treatment of TNBC.

Methods: Firstly, TNBC cells were treated with different concentrations of β-elemene, and screened out an appropriate concentration for subsequent research. Then, through the bioinformatics website, predicted genes that have a binding relationship with β-elemene. Then, the overexpression vector of the selected gene was transfected into the cell. The effects of β-elemene and its target genes on the proliferation and apoptosis of TNBC cells were detected by CCK-8, Edu assay, and flow cytometry, and the senescence of cells was determined by SA-β-gal experiment. Western blotting was used to detect the expression of apoptosis and aging-related proteins.

Results: β-elemene inhibited TNBC cell viability and proliferation in a concentration-dependent manner, and induces apoptosis and senescence. Through the screening of candidate genes, IGF1 was finally determined to be an effective target gene of β-elemene. The expression level of IGF1 was decreased in cells treated with β-elemene. Overexpression of IGF1 significantly alleviated ability of β-elemene to inhibit cell viability, proliferation, and induced cell apoptosis and senescence. In addition, β-elemene inhibited the expression of IGF1R and Bcl-2, and promoted the expression of Cleaved Caspase-3 and senescence-related proteins (p27, p16, p53 and p21), and these effects were reversed by overexpression of IGF1.

Conclusion: β-elemene induced apoptosis and senescence of triple-negative breast cancer cells through IGF1/IGF1R pathway.