@Article{096504018X15179668157803,
AUTHOR = {Ting Yu, Lei Li, Wenyan Liu, Bailiu Ya, Hongju Cheng, Qing Xin},
TITLE = {Silencing of NADPH Oxidase 4 Attenuates Hypoxia Resistance in  Neuroblastoma Cells SH-SY5Y by Inhibiting PI3K/Akt-Dependent Glycolysis},
JOURNAL = {Oncology Research},
VOLUME = {27},
YEAR = {2019},
NUMBER = {5},
PAGES = {525--532},
URL = {http://www.techscience.com/or/v27n5/48567},
ISSN = {1555-3906},
ABSTRACT = {Hypoxia-induced chemoresistance is a major obstacle in the development of effective cancer therapy. In our 
study, the reversal abilities of NADPH oxidase 4 (NOX4) silence on hypoxia resistance and the potential 
mechanism were investigated. Our data showed that the expression of NOX4 was upregulated in human neuroblastoma cells SH-SY5Y under hypoxia condition time dependently. Knockdown of NOX4 expression by 
siRNA inhibited glycolysis induced by hypoxia through decreasing the expression of glycolysis-related proteins (HIF-1 , LDHA, and PDK1), decreasing glucose uptake, lactate production, and ROS production, while 
increasing mitochondria membrane potential. Moreover, NOX4 silence inhibited cell growth under hypoxia 
condition through suppressing cell proliferation and proliferation-related proteins (Ki-67 and PCNA) compared 
with the hypoxia 24 h+siRNA NC group. Further, Western blot experiments exhibited that NOX4 siRNA could 
downregulate the rate of p-Akt/Akt. Treatment with PI3K/Akt signaling activator IGF-1 blocked, while treatment with Akt inhibitor perifosine enhanced the inhibitory effect of si-NOX4 on glycolysis and cell growth. 
In summary, knockdown of NOX4 had the ability of reversing hypoxia resistance, and the major mechanism 
is considered to be the inhibition of glycolysis and cell growth via the PI3K/Akt signaling pathway. Therefore, 
NOX4 could be a novel target against hypoxia resistance in neuroblastoma.},
DOI = {10.3727/096504018X15179668157803}
}