Abstract 7156: Targeting the β-catenin signaling axis in osteosarcoma

Abstract

Abstract Osteosarcoma, an aggressive bone malignancy predominantly affecting children, poses a formidable challenge for therapeutic interventions. Here we evaluated a recently approved FDA drug, PCT, for potential anti-cancer effect in osteosarcoma model. Initial assessments of cytotoxicity encompassing various human and murine osteosarcoma cell lines—OS-17, OS-25, U2OS, SAOS2, MG63, and K7M3—revealed an IC50 ranging 1-3 µM. Subsequent investigations demonstrated significant anti-clonogenic activity and G2M phase cell cycle arrest. Annexin-PI assay showed a notable apoptotic effect of PCT, shedding light on the mode of cell death. Given the pivotal role of β-catenin signaling in human osteosarcoma pathogenesis and metastasis, targeting β-catenin components holds promise for therapeutic intervention. In silico docking studies suggested that PCT may have similar anti-cancer effect compared to β-catenin inhibitors (e.g., MSAB, ICG001). Our western blot analyses in multiple osteosarcoma cell lines demonstrated that PCT inhibits β-catenin pathway. Fluorescence microscopy and PCR analyses substantiated PCT's ability to hinder the nuclear translocation of β-catenin, providing mechanistic insights into its anti-tumor properties. Our preliminary data also suggests that AXL, an upstream regulator of β-catenin pathway, was modulated by PCT. In summary, our findings indicate that PCT exhibits therapeutic potential against osteosarcoma by targeting the β-catenin pathway. Further mechanistic studies are currently underway in our lab. Citation Format: Marina Curcic, Shreyas Gaikwad, Sanjay K Srivastava. Targeting the β-catenin signaling axis in osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7156.