Abstract 2878: Hyperthermia increases the efficacy of aminolevulinic acid-mediated photodynamic therapy in human osteosarcoma cells

Abstract

Abstract Osteosarcoma is a malignant osteoid tumor that arises from mesenchymal cells exhibiting osteoblastic differentiation. Common treatments for this neoplasm include limb-salvage surgery and/or amputation of the affected limb, either of which can substantially decrease quality of life. Therefore, other, less invasive treatments should be explored. Photodynamic therapy (PDT) represents a more targeted, less invasive treatment possibility for osteosarcoma. Previous data from my laboratory demonstrated that aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) can be used to induce significant cell death in human osteosarcoma MG-63 cells in vitro. However, delivering high doses of drugs to deep osteosarcoma tumors could prove difficult, so we aim to explore the use of combination therapies to increase the efficacy of ALA-PDT in human osteosarcoma cells. Previous studies have shown that hyperthermia (increased temperature) can induce cell death in cancer cells. Furthermore, data suggest that combining PDT with hyperthermia can induce cell death in cancer cells synergistically by activating differential death-inducing pathways. However, hyperthermia in combination with ALA-PDT has not been explored in human osteosarcoma. Therefore, we aim to investigate the possibility that hyperthermia in combination with ALA-PDT can increase cell death in human osteosarcoma cells compared to ALA-PDT alone. Data from our lab show that compared to normal body temperature (37°C), cell death in MG-63 human osteosarcoma cells was not significantly increased by mild hyperthermia alone (40°C and 43°C respectively), while moderate hyperthermic temperatures alone (46°C and 49°C) did significantly increase cell death. We also found that at moderately hyperthermic temperatures, ALA-PDT does not increase cell death any further compared to moderate hyperthermia alone. Furthermore, we found that at the mildly hyperthermic temperature of 40°C, cell death was not significantly increased any further by ALA-PDT compared to ALA-PDT alone. However, our data do show that at a temperature of 43°C, hyperthermia plus ALA-PDT increased cell death compared to ALA-PDT alone. Therefore, our data suggest that inducing mild hyperthermia could increase the efficacy of ALA-PDT in human osteosarcoma cells. Citation Format: Paige J. Baugher. Hyperthermia increases the efficacy of aminolevulinic acid-mediated photodynamic therapy in human osteosarcoma cells [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 2878.