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

Background 5-Aminolevulinic Acid (5-ALA) Photodiagnosis (PD) is an effective method to detect residual tumors during glioma surgery. However, the strength of fluorescence differs in every case even in the most malignant glioma such as glioblastoma. Also, false-negative fluorescence may result in tumor residue. We investigated the effect of ultrasound on the intracellular level of protoporphyrin IX (PpIX) and the 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 established cell line, SNB19, U87MG and T98G were used for in vitro experiments. Ultrasound (1MHz, 3W/cm2, Duty cycle 10%) was irradiated on the cultured cells after administration of 5-ALA. The morphological changes of tumor cells were observed. The PpIX levels and the expression of ABCG2 were evaluated. Results The glioma tumor cells showed transient morphological changes and attachment to the culture dish, while most cells survived and were restored to their original morphology within 6 hours. The PpIX expression levels increased in glioma cells after ultrasound irradiation, earlier and higher than 5-ALA alone. Concurrently the expressions of ABCG2, that increased after 5-ALA administration, were relatively reduced in ultrasound irradiated glioma cells. Conclusions The ultrasound irradiation of the malignant gliomas contributes to the stronger 5-ALA induced fluorescence by elevating intracellular PpIX levels. The suppression of ABCG2 expression by ultrasound may be one of the factors which contributes to the PpIX accumulation in glioma cells.