Potential Anti-Cancer Drug 6RK73 Suppresses Ovarian Cancer Growth by Inactivating the AKT1/Sp1 Induced c-Myc Signaling Pathway.

6RK73 is a novel drug designed to target UCHL1 deubiquitinase. Preliminary studies have indicated its anti-cancer activity in breast cancer and renal cell carcinoma. However, its potential anti-cancer effects in other malignancies, including ovarian cancer, remain unclear. In this study, we first determined the IC50 values of 6RK73 in ovarian cancer cell lines OVCAR3 and SKOV3, which were 10.62 μM and 12.90 μM, respectively. Subsequently, we found that 6RK73 effectively inhibited cell proliferation and arrested cell cycle progression in ovarian cancer cells in vitro. Furthermore, 6RK73 suppressed the formation of subcutaneous ovarian cancer tumors in nude mice. Mechanistically, 6RK73 significantly inhibited the AKT1/Sp1/c-Myc signaling pathway, which not only disrupted the interaction between Sp1 and c-Myc but also reduced Sp1 deubiquitination, thereby downregulating c-Myc protein expression. Interestingly, the anti-tumor effects of 6RK73 in ovarian cancer were independent of UCHL1 inhibition. Finally, AKT1 overexpression reversed the 6RK73-mediated suppression of cell proliferation by reactivating the AKT1/Sp1/c-Myc signaling pathway. These findings suggest that 6RK73 is a promising anti-cancer agent that exerts its effects by inactivating AKT1/Sp1/c-Myc signaling in ovarian cancer.