Skip to main content

Open Access Silencing of NADPH Oxidase 4 Attenuates Hypoxia Resistance in Neuroblastoma Cells SH-SY5Y by Inhibiting PI3K/Akt-Dependent Glycolysis

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-1α, 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.

Keywords: Glycolysis; Hypoxia resistance; NADPH oxidase 4 (NOX4); Neuroblastoma; PI3K/Akt

Document Type: Research Article

Affiliations: 1: Department of Physiology, Jining Medical University, Jining, Shandong, P.R. China 2: Department of Diagnosis, Jining Medical University, Jining, Shandong, P.R. China

Publication date: May 7, 2019

More about this publication?
  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.

    From Volume 23, Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics is Open Access under the terms of the Creative Commons CC BY-NC-ND license.

  • Editorial Board
  • Information for Authors
  • Submit a Paper
  • Ingenta Connect is not responsible for the content or availability of external websites
  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content