Home Neoplasma 2016 Neoplasma Vol.63, No.5, p.734-742,2016

Journal info

6 times a year.
Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

Published in English

Editorial Info
Abstracted and Indexed
Submission Guidelines

Select Journal

Webshop Cart

Your Cart is currently empty.

Info: Your browser does not accept cookies. To put products into your cart and purchase them you need to enable cookies.

Neoplasma Vol.63, No.5, p.734-742,2016

Title: Notch1 is associated with the multidrug resistance of hypoxic osteosarcoma by regulating MRP1 gene expression
Author: C. LI, D. GUO, B. TANG, Y. ZHANG, K. ZHANG, L. NIE

Abstract: Hypoxia and Notch signaling pathway are closely related and both participate in cell proliferation and drug resistance of tumors. However, the molecular mechanisms of hypoxia and Notch signaling pathway in cell proliferation and drug resistance of osteosarcoma (OS) remain unclear. In this study, to further evaluate the role of hypoxia and Notch1 on drug resistance of OS, we investigated the influence of inhibiting Notch1 pathway by Notch1 small interference RNA (siRNA) on human MG-63 OS cells in hypoxia. Our data showed that hypoxia promoted OS cell proliferation, induced the G0/G1-S-G2/M phase transition, and increased multidrug resistance of human OS cells. Western blot analysis suggested that hypoxia increased the expression of HIF-1α, Notch1, and multidrug resistance protein-1 (MRP1) in human OS cells. Notch1 siRNA inhibits proliferation and increases apoptosis of hypoxic OS cells. Finally, these hypoxic OS cells can be sensitized to multidrug treatment through inhibition of the Notch protein expression by siRNA. Repression of the Notch protein expression resulted in down-regulation of MRP1 protein. These data support the conclusion that Notch signaling is up-regulated in human OS cells under hypoxia and Notch1 may represent a viable target to overcome chemoresistant OS cells in a hypoxic niche by regulating MRP1 gene expression.

Keywords: hypoxia, HIF-1α, Notch1, multidrug resistance, osteosarcoma
Published online: 09-Sep-2016
Year: 2016, Volume: 63, Issue: 5 Page From: 734, Page To: 742

download file

© AEPress s.r.o
Copyright notice: For any permission to reproduce, archive or otherwise use the documents in the ELiS, please contact AEP.