Cancer stemness kinase inhibitor amcasertib: a promising therapeutic agent in ovarian cancer stem and cancer cell models with different genetic profiles

This study aimed to evaluate the antineoplastic effects of Nanog inhibition, a critical transcription factor associated with pluripotency and its role in ovarian cancer tumorigenesis, using the novel therapeutic agent Amcase rtib in ovarian cancer cells characterized by distinct genetic profiles. The cytotoxicity of Amcasertib was assessed in both ovarian cancer and cancer stem cell models utilizing the Xelligence-RTCA system. The impact of the determined IC50 dose on apoptosis, invasion, migration, epithelial-mesenchym al transition (EMT), cell cycle progression, colony formation, and spheroid growth was evaluated using appropriate analytical techniques. Our findings revealed that Amcasertib exhibited significant antiproliferative effects and induced apoptosis in ovarian cancer and cancer stem cells. Moreover, Amc asertib caused G1 phase arrest and impeded colony formation in MDAH-2774 cells. Additionally, Amcasertib effectively inhibited spheroid growth in OVCAR-3 and OCSC cells. Notably, it demonstrated the ability to suppress invasion and migration in MDAH-2774 and OCSC cells. Furthermore, the suppression of Nanog-mediated stem cell-like features by Amcasertib was particularly pronounced in ER-negative ovarian cancer and cancer stem cells, highlighting its high anticancer efficacy in this subgroup. These results suggest that Amcasertib holds promise as a potential standalone or combination therapy ag ent for the treatment of ER-negative ovarian cancer.
Source: Medical Oncology - Category: Cancer & Oncology Source Type: research