Malignant glioma is one of the most lethal
cancers with rapid progression, high recurrence, and poor prognosis in the central nervous system.
Fatty acid-binding protein 6 (FABP6) is a
bile acid carrier protein that is overexpressed in
colorectal cancer. This study aimed to assess the involvement of FABP6 expression in the progression of
malignant glioma. Immunohistochemical analysis revealed that FABP6 expression was higher in
glioma than in normal brain tissue. After the knockdown of FABP6, a decrease in the migration and invasion abilities of
glioma cells was observed. The phosphorylation of the
myosin light chain was inhibited, which may be associated with migration ability. Moreover, expression levels of invasion-related
proteins,
matrix metalloproteinase-2 (MMP-2) and
cathepsin B, were reduced. Furthermore, tube formation was inhibited in the human umbilical vein endothelial cells with a decreased concentration of
vascular endothelial growth factor (
VEGF) in the
conditioned medium after the knockdown of FABP6. The phosphorylation of the
extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal
kinase (JNK), and p65 were also decreased after FABP6 reduction. Finally, the bioluminescent images and immunostaining of MMP-2, cluster of differentiation 31 (CD31), and the
VEGF receptor 1 (VEGFR1) revealed attenuated
tumor progression in the combination of the FABP6-knocked-down and
temozolomide (TMZ)-treated group in an orthotopic xenograft mouse
tumor model. This is the first study that revealed the impact of FABP6 on the invasion, angiogenesis, and progression of
glioma. The results of this study show that FABP6 may be a potential therapeutic target combined with TMZ for
malignant gliomas.