Paulownin: a promising agent In the fight against the invasion and immune escape in triple-negative breast cancer.

BACKGROUND: Breast cancer is the most prevalent malignancy among females. Paulownin has anti-tumor properties and immune-modulating activities in various cancers; however, its effects on breast cancer remain inadequately understood. AIMS: This study aimed to elucidate the impact of Paulownin on breast cancer and the regulatory mechanisms. METHODS: The cell viability and invasiveness were explored by CCK-8 and Transwell in MDA-MB-231 and BT549 cells. A co-culture system was established using activated CD8+ T cells and MDA-MB-231 or BT549 cells for 24 h. Cell apoptosis was assessed using flow cytometry. The IFN-γ level was analyzed via ELISA. In vivo, the roles of Paulownin were explored in HuPBMC-(M-NSG) mice and detected by immunohistochemistry and western blot. RESULTS: Paulownin decreased the viability of MDA-MB-231 (IC50 = 32.54 μM) and BT549 (IC50 = 38.15 μM) cells. Paulownin reduced the levels of Ki-67 and Vimentin, increased E-cadherin expression, and impaired the invasive capabilities. Paulownin also inhibited PD-L1 expression in MDA-MB-231 and BT549 cells after co-cultured with CD8+ T cells. Paulownin prevented the apoptosis and elevated IFN-γ levels in CD8+ T cells. Additionally, Paulownin suppressed the activity of the AKT/NF-κB signaling pathway. The use of the AKT activator SC79 counteracted the effects of Paulownin on breast cancer cell growth, invasion and immune escape. In vivo, Paulownin inhibited tumor growth, decreased Ki-67 and Vimentin levels, increased E-cadherin, CD8 and IFN-γ levels and suppressed the AKT/NF-κB pathway activation. CONCLUSION: Paulownin restricted breast cancer cell proliferation, invasion, and immune escape. The mechanism may involve the inactivation of the AKT/NF-κB signaling.