Low-intensity pulsed ultrasound (LIPUS) is a noninvasive therapeutic method which gradually being used in clinic including cancers. Exosomes mediate intercellular communication functions in disease development and the potential clinical applications in diagnosis and therapy. However, few studies have discussed the relationship between LIPUS and exosomes. Herein, we show that low intensity (0.6-2.1 W/cm2 or 0.6-3.4 W/cm2) LIPUS promoted exosomes secretion whereas higher intensity (3.4-5.0 W/cm2 or 5.0 W/cm2) LIPUS inhibited exosomes secretion, and this phenomenon is associated with autophagy. Pretreatment with 3-MA or down-regulation of LC3 potentiated low intensity LIPUS's promotion of exosomes secretion and conferred resistance to higher intensity LIPUS's effects on exosomes secretion. Furthermore, pretreatment with PP242 attenuated LIPUS-influenced exosomes secretion while expression of constitutively active Akt (Ad-myr-Akt) elevated LIPUS-influenced exosomes secretion, implying mTOR-dependent mechanism involved. The findings indicate that LIPUS influences exosomes secretion by targeting mTOR-mediated LC3 signaling in SPC-A1 and SPC-A1-BM cells. Our data provided initial evidence to connect LIPUS and secretion of exosomes, and highlight that LIPUS may be exploited in exosome-related diseases.
Keywords: Exosome; Low-intensity pulsed ultrasound; mTOR.
Copyright © 2019. Published by Elsevier Inc.