Effect of bevacizumab on the tight junction proteins of vascular endothelial cells.

This study aimed to investigate how bevacizumab, a vascular endothelial growth factor A (VEGFA) neutralizing antibody applied in clinic, affects the tight junction protein CLDN5 and subsequently influences tumor cell invasion and potential metastasis. Western-blot, quantitative real-time polymerase chain reaction (q-PCR), immunofluorescence and immunohistochemistry revealed that low-dose bevacizumab up-regulated CLDN5, whereas high-dose bevacizumab down-regulated CLDN5. Cell migration, invasion and permeation assay demonstrated that high-dose bevacizumab enhanced the migration, invasion and permeation abilities of human umbilical vein endothelial cells (HUVECs). The migration and permeation abilities of HUVECs were also enhanced by silencing the CLDN5 expression. CLDN5 was regulated by JNK, PI3K and transforming growth factor-β-1 (TGFβ1), and these findings were confirmed by the inhibitor or siRNA of JNK, PI3K and TGFβ1. Our data indicated that high-dose bevacizumab likely increased tumor invasion and potential metastatic abilities by down-regulating CLDN5, which was down regulated by TGFβ1. Low-dose bevacizumab increased CLDN5 expression by up-regulating PI3K and JNK expression. PMID: 31632528 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research