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Nrf2 is the key to chemotherapy resistance in MCF7 breast cancer cells under hypoxia.

Publication ,  Journal Article
Syu, J-P; Chi, J-T; Kung, H-N
Published in: Oncotarget
March 22, 2016

Hypoxia leads to reactive oxygen species (ROS) imbalance, which is proposed to associate with drug resistance and oncogenesis. Inhibition of enzymes of antioxidant balancing system in tumor cells was shown to reduce chemoresistance under hypoxia. However, the underlying mechanism remains unknown. The key regulator of antioxidant balancing system is nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2). In this study, we showed that hypoxia induced ROS production and increased the Nrf2 activity. Nrf2 activation increased levels of its downstream target antioxidant enzymes, including GCLC and GCLM. The Nrf2-overexpressing also confers chemo-resistant MCF7 cells under normoxia. The in vivo mouse model also demonstrated that the chemical inhibition of Nrf2 can increase cisplatin (CDDP) cytotoxicity. Together, these results showed that Nrf2 serves as a key regulator in chemotherapeutic resistance under hypoxia through ROS-Nrf2-GCLC-GSH pathway. Therefore, targeting Nrf2 can be a potential treatment for hypoxia-induced drug resistance in breast cancer cells.

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Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

March 22, 2016

Volume

7

Issue

12

Start / End Page

14659 / 14672

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Signal Transduction
  • NF-E2-Related Factor 2
  • Mice, Inbred ICR
  • Mice
  • Hypoxia
  • Humans
  • Glutamate-Cysteine Ligase
  • Gene Expression Regulation, Neoplastic
 

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Syu, J.-P., Chi, J.-T., & Kung, H.-N. (2016). Nrf2 is the key to chemotherapy resistance in MCF7 breast cancer cells under hypoxia. Oncotarget, 7(12), 14659–14672. https://doi.org/10.18632/oncotarget.7406
Syu, Jhih-Pu, Jen-Tsan Chi, and Hsiu-Ni Kung. “Nrf2 is the key to chemotherapy resistance in MCF7 breast cancer cells under hypoxia.Oncotarget 7, no. 12 (March 22, 2016): 14659–72. https://doi.org/10.18632/oncotarget.7406.
Syu J-P, Chi J-T, Kung H-N. Nrf2 is the key to chemotherapy resistance in MCF7 breast cancer cells under hypoxia. Oncotarget. 2016 Mar 22;7(12):14659–72.
Syu, Jhih-Pu, et al. “Nrf2 is the key to chemotherapy resistance in MCF7 breast cancer cells under hypoxia.Oncotarget, vol. 7, no. 12, Mar. 2016, pp. 14659–72. Pubmed, doi:10.18632/oncotarget.7406.
Syu J-P, Chi J-T, Kung H-N. Nrf2 is the key to chemotherapy resistance in MCF7 breast cancer cells under hypoxia. Oncotarget. 2016 Mar 22;7(12):14659–14672.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

March 22, 2016

Volume

7

Issue

12

Start / End Page

14659 / 14672

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Signal Transduction
  • NF-E2-Related Factor 2
  • Mice, Inbred ICR
  • Mice
  • Hypoxia
  • Humans
  • Glutamate-Cysteine Ligase
  • Gene Expression Regulation, Neoplastic