Vasohibin 1 inhibits Adriamycin resistance in osteosarcoma cells via the protein kinase B signaling pathway.

Vasohibin 1 inhibits Adriamycin resistance in osteosarcoma cells via the protein kinase B signaling pathway.

Oncol Lett. 2018 Apr;15(4):5983-5988

Authors: Huang W, Ren Y, Liu H

Abstract
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: 29556314 [PubMed]

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