Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.3.44 (
P-glycoprotein
)
13,344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Vasohibin (VASH)1 functions as a negative feedback modulator of angiogenesis in vascular endothelial cells. Mesenchymal
VASH1
has been demonstrated to be negatively associated with tumor progression, however studies regarding
VASH1
in tumor cells and its functions remain limited. The function of
VASH1
in osteosarcoma remains unknown. In the present study, it was confirmed that osteosarcoma cells express decreased levels of
VASH1
compared with that expressed by human osteoblast cells. 143B cells with decreased
VASH1
expression revealed increased Adriamycin (ADR) resistance compared with U-2OS cells with increased
VASH1
expression. Subsequent to manipulating
VASH1
expression via transfection, results revealed that overexpression of
VASH1
in 143B cells inhibited
P-glycoprotein
(
P-gp
) expression and ADR resistance significantly; silencing
VASH1
in U-2OS cells enhanced
P-gp
expression and ADR resistance significantly. Research into the molecular mechanism was performed and the results identified that protein kinase B (AKT) and extracellular signal-related kinase signal pathways were both stimulated by
VASH1
, but only AKT inhibitor LY294002 was identified to efficiently counteract increases in
P-gp
expression that had been induced by silencing of
VASH1
in U-2OS cells. ADR resistance promoted by silencing
VASH1
in U-2OS cells was also counteracted by LY294002. In conclusion, the present study confirmed the low expression of
VASH1
in osteosarcoma cells. It was identified that
VASH1
was able to inhibit drug resistance in osteosarcoma cells through regulation of
P-gp
via the AKT signal pathway. This demonstrated a negative regulation function of
VASH1
in osteosarcoma, deepened understanding of the function of
VASH1
in tumors and suggests a basis for further studies in to the functions of
VASH1
.
...
PMID:Vasohibin 1 inhibits Adriamycin resistance in osteosarcoma cells via the protein kinase B signaling pathway. 2955 14