Lawsone inhibits the proliferation and metastasis of residual breast cancer cells after microwave ablation by inducing cellular inhibitory autophagy through NCAPG/AURKB/AKT/mTOR axis

Abstract

Abstract Microwave ablation (MWA) is increasingly used in clinical treatment and research of breast cancer, which has good therapeutic effect on primary and metastatic lesions. However, microwave ablation may lead to residual tumor cells due to incomplete ablation. The biological characteristics of residual tumor cells are unknown, and it is necessary to explore new adjuvant treatment methods to achieve better therapeutic effect. In this study, we demonstrated that the migration ability of residual breast cancer cells was enhanced after microwave ablation, but the proliferation ability was not significantly changed. Lawsone, an active ingredient in Chinese herbal medicine, significantly inhibited the proliferation and metastasis of residual breast cancer cells after microwave ablation in vivo and in vitro, and had synergistic effects with microwave ablation therapy. Mechanistic studies have shown that Lawsone exerts its anti-proliferation and anti-migration ability mainly by targeting NCAPG in residual breast cancer after microwave ablation. In addition, Lawsone-induced cellular inhibitory autophagy also plays a key role in its anticancer effect. In addition, NCAPG interacts with AURKB protein and jointly participates in the regulation of AKT/mTOR pathway to affect autophagy process. In short, these consequences demonstrate that Lawsone exerts its anti-proliferation and anti-metastasis effects on residual breast cancer cells after microwave ablation mainly by inhibiting NCAPG/AURKB/AKT/mTOR axis and inducing inhibitory autophagy, which provides more options for adjuvant therapy after microwave ablation.