The Anti-Tumor Efficacy of Verbascoside on Ovarian Cancer via Facilitating CCN1-AKT/NF-κB Pathway-Mediated M1 Macrophage Polarization

Abstract

BackgroundOvarian cancer (OC) is the leading cause of gynecological cancer-related mortality. Verbascoside (VB) is a phenylpropanoid glycoside from Chinese herbs, with anti-tumour activities. This study aimed to investigate the effects and mechanism of VB on OC.MethodsOC cell lines SKOV3 and A2780 were used in this study. Cell viability, proliferation, and migration were measured using CCK-8, clonogenic, and transwell assays, respectively. Apoptosis and M1/M2 macrophages were detected using flow cytometry. The interaction between VB and CCN1 was predicted by molecular docking. The mRNA expression of CCN1 was detected by RT-qPCR. The protein levels of CCN1, AKT, p-AKT, p65, and p-p65 were determined by western blotting. A xenograft mice model was established for in vivo validation.ResultsVB inhibited OC cell proliferation and migration in a dose-dependent manner, and promoted apoptosis and M1 macrophage polarization. VB downregulated CCN1 and inhibited the AKT/NF-κB pathway. LY294002, an AKT inhibitor, potentiated the anti-tumour effects of VB. CCN1 overexpression weakened the anti-tumour effects of VB and VB + LY294002. In vivo experiments verified that VB inhibited tumour growth and promoted M1 polarization, which is regulated by the CCN1-mediated AKT/NF-κB pathway.ConclusionVB triggers the CCN1-AKT/NF-κB pathway-mediated M1 macrophage polarization for protecting against OC.

The Long Noncoding RNA Gm9866/Nuclear Factor-κB Axis Promotes Macrophage Polarization

“…The results showed that the expression of the M2 macrophage markers MRC1 (macrophage mannose receptor 1) and MRC2 (macrophage mannose receptor 2) was significantly increased after the overexpression of long noncoding RNA Gm9866 (Figures 2(c) – 2(e) ). Previous studies [ 20 , 21 ] have reported that the nuclear factor- κ B family was involved in the process of macrophage polarization. On the basis of the above-mentioned result, it was clear that long noncoding RNA Gm9866 promoted macrophage polarization; hence, we speculated that the nuclear factor- κ B pathway was likely to participate in macrophage polarization promoted by long noncoding RNA Gm9866.…”

“…These results laid a foundation for more direct and in-depth research on the molecular mechanism of long noncoding RNA Gm9866. Some previous studies [20,21,38,[43][44][45] have reported that the nuclear factor-κB family is involved in macrophage polarization. We therefore speculated that long noncoding RNA Gm9866 may act through the nuclear factor-κB signaling pathway.…”

Development and validation of a novel anoikis-related gene signature for predicting prognosis in ovarian cancer

“…It has been shown that M1 macrophage exhibits anti-tumor effects, whereas M2 pro-tumor effects [ 54 ]. This unique property of NK cells and their ability to enhance T cell responses and antibodies supports NK cells as a therapeutic hope in the fight against cancer, as they have the potential to kill tumor cells in a variety of ways without prior sensitisation [ 55 ].…”