摘要：SummaryCancer stem cells, quiescent and drug resistant, have become a therapeutic target. Unlike high-intensity focused ultrasound directly killing tumor, low-intensity pulsed ultrasound (LIPUS), a new noninvasive physical device, promotes pluripotent stem cell differentiation and is primarily applied in tissue engineering but rarely in oncotherapy. We explored the effect and mechanism of LIPUS on glioma stem cell (GSC) expulsion from quiescence. Here, we observed that LIPUS led to attenuated expression of GSC biomarkers, promoted GSC escape from G0 quiescence, and significantly weakened the Wnt and Hh pathways. Of note, LIPUS transferred sonomechanical energy into cytochromecand B5 proteins, which converted oxygen molecules into singlet oxygen, triggering telomere crisis. Thein vivoandin vitroresults confirmed that LIPUS enhanced the GSC sensitivity to temozolomide. These results demonstrated that LIPUS “waked up” GSCs to improve their sensitivity to chemotherapy, and importantly, we confirmed the direct targeted proteins of LIPUS in GSCs.Graphical abstractDisplay OmittedHighlights•LIPUS “waked quiescent GSCs up” and enhanced the sensitivity of temozolomide•LIPUS-generated singlet oxygen damaged telomeres, reducing GSCs stemness•Cytochrome B5 andcare targets for LIUPS energy transferMedical device; Cell biology; Stem cells research; Cancer
