The Propranolol Induces Apoptosis in Epithelial Ovarian Cancer Cells by Inhibiting the AKT Signaling Pathway

Abstract

Objective: This study aimed to investigate whether propranolol affects ovarian cancer (OV) cell viability and apoptosis through inhibition of the AKT signaling pathway.

Methods: SKOV3 human epithelial ovarian cancer cells were treated with 0, 25, 50, 100, 200, and 400 μM propranolol hydrochloride for 0, 24, 48, and 72 hours. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8). After treating SKOV3 cells with 0, 50, 100, and 200 μM propranolol for 24 hours, quantitative real-time PCR (qRT-PCR) was used to measure mRNA levels of BCL-2, BAX, and AKT. Western blotting was performed to detect caspase-3 and AKT protein expression. Additionally, SKOV3 cells were co-treated with propranolol and either the AKT activator N-oleoyl glycine or the AKT inhibitor AZD5363 for 24 hours. AKT protein expression and cell proliferation were evaluated by Western blot and CCK-8 assay, respectively.

Results: Propranolol significantly inhibited SKOV3 cell proliferation in a concentration- and time-dependent manner (P < 0.001) and induced apoptosis, as evidenced by upregulation of BAX mRNA and caspase-3 protein, and downregulation of BCL-2 mRNA and AKT mRNA/protein (P < 0.01). The AKT inhibitor synergistically enhanced propranolol-induced suppression of cell viability and AKT protein expression (P < 0.001), whereas the AKT activator significantly reversed the inhibitory effects of propranolol on AKT and cell viability (P < 0.001).

Conclusions: Propranolol-induced apoptosis of OV is mediated by inhibiting the AKT signaling pathway.