Investigating the Effects of ONC206 Alone and in Combination with Cisplatin on Ovarian Cancer Cell Models

Ovarian cancer (OC) is the most lethal gynecologic malignancy worldwide, with high rates of disease relapse posing a significant therapeutic challenge. Consequently, there is an urgent need to develop novel treatments for OC. This study aims to evaluate the effects of the novel imipridone, ONC206, both as a monotherapy and in combination with the standard of care chemotherapy drug, cisplatin (CDDP), on human OC cell lines. In order to study the effect of ONC206 and CDDP on ovarian cancer, two cell lines, OVCAR-420 and SKOV-3, were used in this study. Cell proliferation was assessed using MTT assay while cell viability was evaluated using the trypan blue exclusion assay. Cell migration was examined using the wound healing assay. To investigate the effects of both treatments, alone or in combination on the stem-cell-like population of OC cells, the sphere-forming assay was employed. Our results revealed that ONC206, alone or in combination with CDDP, exerts a potent anti-proliferative effect on both OVCAR-420 and SKOV-3 cells, as shown in the MTT and trypan blue exclusion assays. Interestingly, a synergistic effect was observed when ONC206 was combined with CDDP, enhancing the overall anti-cancer efficacy. Additionally, ONC206 alone or in combination with CDDP inhibited the migratory ability of the ovarian cancer cells. Furthermore, the activity of ovarian cancer stem cells was inhibited when cells were treated with ONC206 alone or in combination with CDDP, as shown in the significant decrease in both the size and the sphere-forming ability of ovarian cancer stem cells in the 3D culture model. Our results highly suggest the potential of imipridones as a new class of therapeutics in ovarian cancer management. Among these, ONC206 shows nanomolar potency, highlighting its potential as a standalone therapy or in combination with existing treatment regimens.