title: Increasing of blood-tumor barrier permeability through paracellular pathway by low-frequency ultrasound irradiation in vitro.
abstract: The research was conducted to study the increase of blood-tumor barrier (BTB) permeability through paracellular pathway by low-frequency ultrasound (LFU) irradiation in vitro. LFU (frequency=1.0 MHz) was performed to irradiate BTB model from the co-culture of rat C6 glioma cells and rat brain microvascular endothelial cells (RBMECs). The permeability of BTB was measured by transendothelial electrical resistance (TEER) and flux of horseradish peroxidase (HRP) assays after LFU irradiation. Western-blotting, immunohistochemistry, and immunofluorescence assays were used to investigate the changes of expressions and distributions of tight junction (TJ)-associated proteins ZO-1, occludin, and claudin-5. The TEER value began to decrease, and the minimum value appeared at 2 h, then gradually returned to the original level at 24 h after LFU irradiation. With time, flux of HRP gradually increased and reached the peak 2 h after LFU irradiation. The expressions of ZO-1, occludin, and claudin-5 in RBMECs decreased, and decreased most significantly at 2 h, then gradually restored to the original level at 24 h. Meanwhile, they were discontinuously distributed in the cellular boundaries after LFU irradiation. In summary, the expression of TJ-associated proteins was down-regulated, TJ was opened, and the permeability of BTB was increased through paracellular pathway by LFU irradiation.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.
authors.forename: Lilin
authors.initials: L
authors.lastname: Fan
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Liu
authors.forename: Haoqiang
authors.initials: H
authors.lastname: Ying
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Libo
authors.initials: L
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D002470:Cell Survival; D002478:Cells, Cultured; D062507:Claudin-5; D018920:Coculture Techniques; D017097:Electric Impedance; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D062793:Occludin; D010539:Permeability; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000737:chemistry / Q000378:metabolism; D014465:Ultrasonics / Q000379:methods*; D019043:Vascular Neoplasms / Q000473:pathology*; D062826:Zonula Occludens-1 Protein
chemical_list: D062507:Claudin-5; C491510:Cldn5 protein, rat; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein