Atorvastatin Calcium Enhances Ferroptosis in Breast Cancer Cells Through Mechanisms Involving DECR1.

BACKGROUND

Breast cancer is currently the most prevalent malignancy among females, representing a substantial threat to both physical and psychological health. Moreover, its incidence rate continues to rise annually. Therefore, screening potential therapeutic targets and developing candidate drugs for breast cancer treatment holds significant clinical implications.

METHODS

In this study, in silico methods were used to identify potential therapeutic targets of fatty acid metabolism-related genes in breast cancer and to screen potential drugs using molecular docking. In addition, Cell Counting Kit-8 (CCK-8) and Transwell assays were utilized to analyze the effect of atorvastatin calcium (AC) on the malignant phenotype of breast cancer cells. Furthermore, the effects of AC-induced ferroptosis in tumor cells were evaluated using transmission electron microscopy, ROS, Fe2+, and Liperfluo probes, and the potential molecular mechanisms were explored through real-time qPCRand western blotting.

RESULTS

2,4-Dienoyl-CoA Reductase 1 (DECR1) overexpression was related to a dismal prognostic outcome in breast cancer patients. AC interfered with breast cancer cell proliferation and invasion, potentially through its effects in DECR1 expression, while suppressing tumor growth in vivo. In addition, AC demonstrated antitumor effects, possibly through the downregulation of DECR1 and the upregulation of Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4), which may contribute to the induction of ferroptosis in tumor cells.

CONCLUSIONS

DECR1 is associated with breast cancer progression and may serve as a potential therapeutic indicator, and AC plays an antitumor role by modulating DECR1 expression and promoting ACSL4-mediated ferroptosis. Therefore, AC may be considered a potential candidate drug for treating breast cancer.