Silencing of NADPH oxidase 4 attenuates hypoxia resistance in neuroblastoma cells SHSY-5Y by inhibiting PI3K/Akt-dependent glycolysis.

Silencing of NADPH oxidase 4 attenuates hypoxia resistance in neuroblastoma cells SHSY-5Y by inhibiting PI3K/Akt-dependent glycolysis. Oncol Res. 2018 Feb 09;: Authors: Yu T, Li L, Liu W, Ya B, Cheng H, Xin Q 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 the hypoxia resistance and the potential mechanism were investigated. Our data showed that the expression of NOX4 was up-regulated in human neuroblastoma cells SHSY-5Y 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-1α, LDHA, PDK1), decreasing glucose uptake, lactate production, ROS production while increasing mitochondria membrane potential. Moreover, NOX4 silence inhibited cell viability under hypoxia condition through suppressing cell proliferation and proliferation related proteins (Ki67, PCNA) compared with hypoxia 24h + siRNA NC group. Further, western blot experiments exhibited that NOX4 siRNA could down-regulate the rate of p-Akt/Akt. Treatment with PI3K/Akt signaling activator IGF-I blocked while treatment with Akt inhibitor Perifosine enhanced the inhibitory effect of si-NOX4 on glycolysis and cell viability. In summary, knockdown of NOX4 had an ability of reversing hypoxia resistance, and the major...
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research