STEM-16SONODYNAMIC 5-ALA PLUS ULTRASOUND THERAPY AUGMENTS ANTI-TUMOR EFFECTS IN THE ONCOGENE KNOCK-IN GLIOMA STEM CELLS

Abstract

STEM-16. SONODYNAMIC 5-ALA PLUS ULTRASOUND THERAPY AUGMENTS ANTI-TUMOR EFFECTS IN THE ONCOGENE KNOCK-IN GLIOMA STEM CELLS Kenji Shono, Teruyoshi Kageji, Yoshihumi Mizobuchi, Toshitaka Fujihara, Keiko Kitazato, Kohei Nakajima, Hideo Mure, Kazuyuki Kuwayama, and Shinji Nagahiro; Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima UniversityGraduateSchool, Tokushima City,Tokusima Prefecture, Japan INTRODUCTION: To overcome the chemoand radiation resistance of glioblastoma multiforme (GBM), new therapeutic strategies are needed. Sonodynamic therapy (SDT) is efficacious in several types of tumor and cancer. However, there are few studies in oncogene knock-in glioma stem cells (GSCs), which are thought to be implicated in the therapeutic resistance of GBM. We tested our hypothesis that SDT is effective in GSCs and GBM cells. METHODS: Using GSCs and U251 MG cells we assessed the efficacy of SDT in vitro. We also studied the anti-tumor effects of SDT in GSC-bearing mice. We compared the efficacy of SDT delivered in a single ultrasound session (1 MHz, 2W/cm) with the results obtained with 5-ALA delivered at 1 mM/well. RESULTS: While no significant effects were observed when cells were exposed to 5-ALA, ultrasound-treated cells lost viability immediately after exposure. SDT enhanced the effects of ultrasonography. Our findings suggest that SDT may be effective in GBM cells and GSCs. CONCLUSION: Ours is the first study to show the efficacy of SDT in GSCs. The mechanisms mediated by SDT and by photodynamic therapy may be different. Studies are underway to confirm the beneficial effects of SDT in GSC-bearing mice and to elucidate the mechanisms underlying its efficacy. Neuro-Oncology 17:v208–v213, 2015. doi:10.1093/neuonc/nov234.16 Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.