Assessing the Effects of ONC 206 Alone and in Combination with Cisplatin (CDDP) on Ovarian Cancer cell lines

Abstract

Ovarian cancer (OC) is considered the most lethal gynecologic malignancy worldwide with chemoresistance along with disease relapse, presenting major challenges. Therefore, developing novel therapies for OC is of utmost priority. Cisplatin (CDDP) is considered as the standard chemotherapy drug used in OC, though patients often develop resistance. Imipridones, a novel class of anti-cancer compounds, may be a novel therapeutic strategy that also aims to overcome this resistance. Therefore, this study aims to assess the effects of the Imipridone ONC 206, alone and in combination with CDDP on human OC cell lines. Methods: Two ovarian cancer cell lines, OVCAR-420 and SKOV-3, were used in this study, using both two-dimensional (2D) and three-dimensional assays (3D). The 2D assays included the MTT assay, trypan blue exclusion assay and wound healing assay to assess the effects of ONC206 alone and in combination with CDDP, on cell proliferation, viability and migratory ability, respectively. Additionally, the 3D sphere-forming assay was performed to examine the effects of both drugs on targeting the enriched population of OC stem cells. Results: Our MTT assay results demonstrated that ONC 206, both alone and in combination with CDDP, significantly inhibited the proliferation of OVCAR-420 and SKOV-3 cells. These findings were further validated using the trypan blue exclusion assay. A synergistic effect was observed when the two drugs were combined, enhancing their overall effectiveness. ONC 206 alone and in combination with CDDP resulted in incomplete wound closure in both cell lines Notably, in a 3D culture model, the sphere formation assay confirmed that ONC 206, either by itself or with CDDP, reduced both the size and sphere-forming ability of ovarian cancer stem cells. Conclusion: Our findings highlight the potential anti-cancer effects of Imipridones, particularly ONC206. Interestingly, ONC206 shows a remarkable synergy with cisplatin (CDDP), enhancing its efficacy even in resistant ovarian cancer cell lines, suggesting that this combination could overcome some of the limitations of traditional chemotherapy. As a result, ONC206 emerges as a promising candidate in future OC clinical trials.