Mechanism of low-frequency ultrasound in opening blood-tumor barrier by tight junction.
The clinical chemotherapy of brain tumors has been limited by the blood-tumor barrier (BTB). Low-frequency ultrasound (LFU) in combination with microbubbles might be a useful method for local drug delivery. However, the underlying mechanism remains unclear. In this study, we asked whether LFU changed the permeability of BTB by regulating the tight junction-related proteins. The permeability of BTB was evaluated by Evans blue dye, and the protein and mRNA expression levels of tight junction-related proteins claudin-5, occludin, and ZO-1 were determined by immunohistochemical staining, RT-PCR, and western blot assays. We found that the permeability of BTB increased significantly after LFU exposure in the presence of Optison. The mRNA and protein expression levels of claudin-5, occludin, and ZO-1 decreased significantly at 3 h, restored gradually and nearly recovered after 12 h. The correlation between the increase of BTB permeability and the reduction of tight junction-related proteins suggests that LFU combined with microbubbles may be involved in the opening of the BTB by the tight junction-related proteins.
Shang
Xiuli
X
Department of Neurology, First Affiliated Hospital, China Medical University, Shenyang, 110001, People's Republic of China.
Wang
Ping
P
Liu
Yunhui
Y
Zhang
Zhen
Z
Xue
Yixue
Y
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000648:ultrastructure; D062507:Claudin-5; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D045423:Microbubbles; D062793:Occludin; D010539:Permeability; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; 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
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