-Original-

Ultrasound Modulates Fluorescence Strength and ABCG2 mRNA Response to Aminolevulinic Acid in Glioma Cells

Tadashi Higuchi¹, Fumio Yamaguchi², Takayuki Asakura¹, Daizo Yoshida^1,3, Yumiko Oishi⁴ and Akio Morita¹

¹Department of Neurological Surgery, Nippon Medical School, Tokyo, Japan
²Department of Neurosurgery for Community Health, Nippon Medical School Graduate School, Tokyo, Japan
³Rihabilipark Itabashi Hospital, Tokyo, Japan
⁴Department of Biochemistry & Molecular Biology, Nippon Medical School, Tokyo, Japan

Background: 5-Aminolevulinic Acid (5-ALA) photodiagnosis (PD) is an effective method to detect residual tumors during glioma surgery. However, fluorescence strength differs in malignant gliomas, and false-negative fluorescence may result in tumor residue. We investigated the effect of ultrasound on the intracellular level of protoporphyrin IX (PpIX) and expression level of ATP-binding cassette transporter 2 (ABCG2), which is thought to act as a membrane efflux pump of PpIX from cytosol.
Methods: The malignant glioma cell lines SNB19, U87MG, and T98G were used for in vitro experiments. Cultured cells underwent ultrasound irradiation (1 MHz, 3 W/cm², duty cycle 10%) after administration of 5-ALA, and morphological changes in tumor cells were observed. PpIX levels and ABCG2 expression were evaluated.
Results: The glioma tumor cells showed transient morphological changes and detachment from the culture dish; however, most cells survived and reverted to their original morphology within 6 hours. PpIX expression levels increased in glioma cells after ultrasound irradiation, and the increase was earlier and greater than that for 5-ALA alone. ABCG2 expressions increased after 5-ALA administration but were lower in ultrasound-irradiated glioma cells.
Conclusions: Ultrasound irradiation of malignant gliomas contributes to stronger 5-ALA-induced fluorescence by elevating intracellular PpIX levels. Suppression of ABCG2 expression by ultrasound may contribute to PpIX accumulation in glioma cells.

J Nippon Med Sch 2020; 87: 310-317

Keywords
5-ALA, protoporphyrin IX, ABCG2, malignant glioma, ultrasound

Correspondence to
Fumio Yamaguchi, Department of Neurosurgery for Community Health, Nippon Medical School Graduate School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
fyamaguc@nms.ac.jp

Received, January 17, 2020
Accepted, January 24, 2020