Ursolic acid affects autophagy and apoptosis of breast cancer through PLK1 via AKT/mTOR signaling pathway.

Abstract

Breast cancer poses a significant threat to women's health globally, exhibiting the greatest incidence and fatality rates among female cancers. Chemotherapy is frequently employed in the clinical management of breast cancer. While the majority of patients require novel chemotherapeutic agents due to treatment resistance. We sought to examine the impact of ursolic acid (UA) on apoptosis and autophagy levels in breast cancer through Polo-like Kinase 1 (PLK1) via the AKT/mTOR signaling pathway. Tamoxifen (TAM) and adriamycin (ADM) served as positive control agents. In vitro experiments, the MTT assay was utilized to evaluate the viability of MCF-7/MDA-MB-231 cells, flow cytometry and JC-1 staining to analyze apoptosis, electron microscopy and MDC staining to scrutinize autophagy, and Western blot (WB) to measure the expression of pertinent proteins. In vivo research utilized the BALB/c mouse breast cancer model established with 4T1, comparing the volume and weight of transplanted tumors across several groups. Tumor necrosis was identified using HE staining, anti-apoptotic protein Bcl-2 expression was assessed via IHC labeling, and protein expression was evaluated using WB. UA suppressed tumor proliferation in BALB/c mice models of breast cancer. Tumor proliferation was markedly suppressed in the TAM and medium/high-dose UA cohorts. HE staining demonstrated significant necrosis, while IHC/WB analysis validated that UA or UA combined with Volasertib may reduce levels of Bcl-2, PLK1, p-AKT/AKT, and p-mTOR/mTOR, in conjunction with increased LC3 II/I. In conclusion, the study revealed that UA may affect the apoptosis and autophagy of breast cancer through PLK1 via AKT/mTOR signaling pathway.