Repurposing of Spironolactone Towards Upregulation of the Expression of NKG2D Ligands in Metastatic Osteosarcoma Mouse Model

Abstract Osteosarcoma (OS) is the most common bone cancer affecting children with a high-grade malignancy characterised by severe lung metastases. Targeting tumour cell surface antigens have proven effective as alternative cancer treatments. Natural killer (NK) cells efficiently recognize and kill tumour cells through several mechanisms including the expression of ligands for NK cell-activating receptors. The NKG2D and its ligands are required for NK cells-mediated immune response to malignancies. Nonetheless, such therapeutic strategy remains elusive towards solid tumours, particularly metastatic OS. Here, we examine the efficiency of NK cells in tumour recognition by way of a repurpose drug, spironolactone (SPIR). The SPIR-treated cells (HOS-143B) were inoculated into male NOG mice to establish the metastatic OS model. The tumour was apparent in both group and lung metastasis was confirmed with H&E staining. Flow cytometry analysis showed a significant increase in the expression of the NKG2D ligands in tumour tissue induced by SPIR-treated OS-cells compared to control group. These findings revealed an alternative role of SPIR, as an immunosensitizing drug, indicated by the upregulation of NK cells ligands in the metastatic OS model. Hence, the repurposing of SPIR provides a promising approach towards a novel strategy of onco-immunotherapy for OS.