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Research Article

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Noriko Moricorresponding author
Yelena Mironchik
Flonné Wildes
Sherry Y. Wu
Kanami Mori
Balaji Krishnamachary
Zaver M. Bhujwalla


Our purpose was to understand the effects of normoxia or hypoxia on 5-fluorouracil  (5-FU) treatment in triple negative breast cancer (TNBC) cells, and characterize the molecular changes in hypoxia inducible factors (HIFs) and cyclooxygenase-2 (COX-2) following treatment.  Cell viability and protein levels of HIFs and COX-2 were determined after wild type and HIF silenced MDA-MB-231 cells, and wild type SUM-149 cells, were treated with 5-FU under normoxia or hypoxia.  5-FU reduced cell viability to the same levels irrespective of normoxia or hypoxia.  HIF silenced MDA-MB-231 cells showed comparable changes in cell viability, supporting observations that hypoxia and the HIF pathways did not significantly influence cell viability reduction by 5-FU.  Our data suggest that HIF-2aaccumulation may predispose cancer cells to cell death under hypoxia.  SUM-149 cells that have higher COX-2 and HIF-2afollowing 24 h of hypoxia, were more sensitive to 96 h of hypoxia compared to MDA-MB-231 cells, and were more sensitive to 5-FU than MDA-MB-231 cells.  COX-2 levels changed with hypoxia and with 5-FU treatment but patterns were different between the two cell lines.  At 96 h, COX-2 increased in both untreated and 5-FU treated cells under hypoxia in MDA-MB-231 cells.  In SUM-149 cells, only treatment with 5-FU increased COX-2 at 96 h of hypoxia.  Cells that survive hypoxia and 5-FU treatment may exhibit a more aggressive phenotype.  Our results support understanding interactions between HIF and COX-2 with chemotherapeutic agents under normoxia and hypoxia, and investigating the use of COX-2 inhibitors in these settings.

5-FU, COX-2, HIF, Hypoxia, TNBC

Article Details

Supporting Agencies
This work was supported by National institutes of health (NIH) R01CA82337
How to Cite
Mori, Noriko, Yelena Mironchik, Flonné Wildes, Sherry Wu, Kanami Mori, Balaji Krishnamachary, and Zaver Bhujwalla. 2020. “HIF and COX-2 Expression in Triple Negative Breast Cancer Cells With Hypoxia and 5-Fluorouracil”. Current Cancer Reports 2 (1), 54-63.


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