本研究旨在探讨低强度超声（LIUS）结合低浓度三氧化二砷（ATO）是否能够抑制胶质瘤的增殖，并进一步阐明其潜在机制。通过CCK8、EdU和流式细胞术检测ATO和LIUS单独或联合对胶质瘤的影响。采用免疫印记扩散检测细胞凋亡相关蛋白的表达变化和其对EGFR/AKT/mTOR通路的影响。利用原位移植模型在体内验证ATO和LIUS的效果，观察瘤体大小、脑组织中砷含量、生存率和免疫组织化学变化。LIUS增强了ATO对胶质瘤增殖的抑制效果，EGF逆转了ATO和LIUS诱导的增殖抑制和蛋白质变化。ATO与LIUS联合治疗的抗胶质瘤效应与EGFR激活抑制引起的下游AKT/mTOR通路变化相关，增强了U87MG和U373细胞的凋亡。体内实验显示与其他组相比，联合治疗组脑组织中的砷含量显著增加，瘤体大小减小，生存时间延长，免疫组织化学蛋白质变化趋势与体外实验结果一致。本研究表明LIUS能够以安全剂量使ATO发挥抗胶质瘤作用，通过抑制EGFR的活化和下游AKT/mTOR通路来调节细胞凋亡。LIUS与ATO结合是治疗胶质瘤的一种有前景的新方法，可以改善患者预后。版权所有 © 2023. Elsevier Inc. 发表

This study aimed to explore whether low-intensity ultrasound (LIUS) combined with low-concentration arsenic trioxide (ATO) could inhibit the proliferation of glioma and, if so, to clarify the potential mechanism.The effects of ATO and LIUS alone or in combination on glioma were examined by CCK8, EdU, and flow cytometry assays. Western blot analysis was used to detect changes in expression of apoptosis-related proteins and their effects on the EGFR/AKT/mTOR pathway. The effects of ATO and LIUS were verified in vivo in orthotopic xenograft models, and tumor size, arsenic content in brain tissue, survival, and immunohistochemical changes were observed.LIUS enhanced the inhibitory effect of ATO on the proliferation of glioma, and EGF reversed the proliferation inhibition and protein changes induced by ATO and LIUS. The anti-glioma effect of ATO combined with LIUS was related to downstream AKT/mTOR pathway changes caused by inhibition of EGFR activation, which enhanced apoptosis of U87MG and U373 cells. In vivo experiments showed significant increases in arsenic content in brain tissue, as well as decreased tumor sizes and longer survival times in the combined treatment group compared with other groups. The trends of immunohistochemical protein changes were consistent with the in vitro results.This study showed that LIUS enables ATO to exert anti-glioma effects at a safe dose by inhibiting the activation of EGFR and the downstream AKT/mTOR pathway to regulate apoptosis. LIUS in combination with ATO is a promising novel method for treating glioma and could improve patient prognosis.Copyright © 2023. Published by Elsevier Inc.