{"doi":"10.25082/ccr.2020.01.005","title":"HIF and COX-2 expression in triple negative breast cancer cells with hypoxia and 5-fluorouracil","abstract":"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.","journal":"Current Cancer Reports","year":2020,"id":107633,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":365354,"name":"Yelena Mironchik","orcid":null,"position":1,"is_corresponding":false},{"id":365433,"name":"Flonné Wildes","orcid":null,"position":2,"is_corresponding":false},{"id":274976,"name":"Sherry Y. Wu","orcid":"0000-0002-6051-4252","position":3,"is_corresponding":false},{"id":516808,"name":"Kanami Mori‐Yasumoto","orcid":"0000-0002-9718-0823","position":4,"is_corresponding":false},{"id":299501,"name":"Balaji Krishnamachary","orcid":"0000-0001-6137-5832","position":5,"is_corresponding":false},{"id":272184,"name":"Zaver M. Bhujwalla","orcid":"0000-0002-6617-9360","position":6,"is_corresponding":false},{"id":517275,"name":"Noriko Mori","orcid":null,"position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T23:12:34.898963Z","pmid":"35814639","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}