CUDC-907 exhibits potent antitumor effects against ovarian cancer through multiple in vivo and in vitro mechanisms.

Abstract

Purpose: CUDC-907 is a promising dual-target inhibitor of the HDAC and PI3K signaling pathways, with demonstrated therapeutic effects in a range of malignant tumors. However, its potential application in ovarian cancer (OC) has not been fully explored yet. In this study, we sought to investigate the efficacy of CUDC-907 in treating OC, both in vitro and in vivo.

Methods: Here, we examined the correlation between PI3K or HDAC expression and the prognosis of OC patients using the GEPIA database. RNA-Seq analysis was performed on OC cells treated with CUDC-907.To assess various cellular processes, including proliferation, migration, invasion, apoptosis, and cell cycle, we performed a series of assays, including the CCK8, EDU, wound healing, cell invasion, and flow cytometry assays. Real-time quantitative PCR and western blotting were performed to measure the expressions of target genes. Additionally, we utilized the SKOV3 xenograft tumor model to investigate the inhibitory effects of CUDC-907 on tumor growth in vivo.

Results: Bioinformatics analyses revealed that up-regulated HDAC and PI3K were significantly correlated with patients' poor survival in OC. In vivo and in vitro experiments have demonstrated that CUDC-907 could inhibit the proliferation of OC cells by inhibiting the PI3K and HDAC pathways to down-regulate the expression of c-Myc, and induce cell apoptosis by inhibiting the PI3K/AKT/Bcl-2 pathway, and up-regulate p21 to induce G2 /M phase arrest.

Conclusion: Our results showed that CUDC-907 had powerful anti-tumor effects on OC, which could provide a theoretical and experimental basis for the application of CUDC-907 in the therapy of OC.