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This article is the authors’ final published version in Cells, Volume 10, Issue 7, June 2021, Article number 1647.

The published version is available at Copyright © Liu et al.


Development of resistance to therapy in ovarian cancer is a major hinderance for therapeutic efficacy; however, new mechanisms of the resistance remain to be elucidated. NADPH oxidase 4 (NOX4) is responsible for higher NADPH activity to increase reactive oxygen species (ROS) production. In this study, we showed that higher levels of NOX4 were detected in a large portion of human ovarian cancer samples. To understand the molecular mechanism of the NOX4 upregulation, we showed that NOX4 expression was induced by HIF-1α and growth factor such as IGF-1. Furthermore, our results indicated that NOX4 played a pivotal role in chemotherapy and radiotherapy resistance in ovarian cancer cells. We also demonstrated that NOX4 knockdown increased sensitivity of targeted therapy and radiotherapy through decreased expression of HER3 (ERBB3) and NF-κB p65. Taken together, we identified a new HIF-1α/NOX4 signal pathway which induced drug and radiation resistance in ovarian cancer. The finding may provide a new option to overcome the therapeutic resistance of ovarian cancer in the future.

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Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

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