Fluzoparib disrupts Golgi apparatus to inhibit O-GlcNAcylation and nuclear translocation of β-catenin to attenuate ovarian cancer invasion and metastasis

Ovarian Cancer is one of the most common malignant tumors of the female reproductive system, with the majority of patients already presenting with peritoneal dissemination and Other metastases at the time of initial diagnosis. Fluzoparib (FZ) is the first domestically developed PARP Inhibitor in China. The efficacy of FZ in inhibiting the invasiveness and metastasis of ovarian Cancer remains uncertain, and its potential mechanisms are yet to be elucidated. O-GlcNAcylation is an important post-translational modification that is crucial for the function and localization of proteins, with the Golgi apparatus serving as an important subcellular compartment involved in O-GlcNAcylation-related protein regulation. However, the regulatory effects of FZ on the Golgi apparatus and O-GlcNAcylation remain unclear. Here, we found that FZ significantly reduces the viability, proliferative capacity, invasiveness, and metastatic potential of ovarian Cancer cells while promoting Apoptosis. In vivo, FZ decreases the formation of ascites in mice and diminishes peritoneal metastatic implantation without causing significant damage to major organs. Mechanistically, FZ disrupts the morphology and function of the Golgi apparatus, inhibits the O-GlcNAcylation of β-catenin, and promotes competitive phosphorylation of β-catenin, thereby preventing its translocation to the nucleus and ultimately inhibiting the invasion and metastasis of ovarian Cancer. In summary, this study reveals that FZ disrupts the Golgi apparatus and inhibits the O-GlcNAcylation and nuclear translocation of β-catenin, thereby preventing the invasion and metastasis of ovarian Cancer.

Fluzoparib; Golgi apparatus; O-GlcNAcylation; Ovarian cancer; Β-Catenin.