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Updated: Jun 28, 2026

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Published on: August 12, 2015
The malignant phenotype of breast cancer cells is reduced by COX-2 silencing
Ioannis Stasinopoulos1, Noriko Mori, Zaver M Bhujwalla
1The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Abstract:
The cyclooxygenase (COX) pathway is currently targeted for therapeutic intervention in different cancers. We have previously shown that silencing of COX-2 in the poorly differentiated metastatic breast cell line MDA-MB-231 by RNA interference markedly delayed tumor onset and inhibited metastasis. To understand the functional effects of COX-2 silencing underlying the inhibition of tumor growth and metastasis previously reported, we investigated changes in these cells for a number of cancer-associated phenotypes. Cyclooxygenase-2-silenced cells were less able to acidify tissue culture medium, a response that could partly be attributed to decreased lactate production or export detected by reduced lactate in the medium. Consistent with the significantly reduced transcript levels of hyaluronan synthase 2, an enzyme responsible for the total level of hyaluronan secreted by these cells, COX-2 silencing resulted in lower hyaluronan levels secreted in culture medium. Inhibition of human umbilical vein endothelial cell network association in a coculture assay was also observed in COX-2-silenced cells. These data highlight the functional role of COX-2 in pathways that mediate increased malignancy.
Insights
Silencing cyclooxygenase-2 (COX-2) in metastatic breast cancer cells reduces malignancy. This inhibition affects medium acidification, lactate production, hyaluronan secretion, and endothelial cell network formation, highlighting COX-2
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The cyclooxygenase (COX) pathway, particularly COX-2, is a therapeutic target in various cancers.
- Previous studies demonstrated that silencing COX-2 in MDA-MB-231 breast cancer cells delays tumor onset and inhibits metastasis.
Purpose of the Study:
- To elucidate the functional mechanisms by which COX-2 silencing impacts cancer-associated phenotypes.
- To investigate the role of COX-2 in regulating cellular processes critical for tumor growth and metastasis.
Main Methods:
- RNA interference was used to silence COX-2 expression in MDA-MB-231 cells.
- Assays were performed to measure medium acidification, lactate production/export, hyaluronan secretion, and endothelial cell network formation.
Main Results:
- COX-2-silenced cells exhibited reduced medium acidification and decreased lactate levels.
- Significant reduction in hyaluronan synthase 2 transcript levels and lower secreted hyaluronan were observed.
- Inhibition of human umbilical vein endothelial cell network formation was noted in COX-2-silenced cells.
Conclusions:
- COX-2 plays a crucial functional role in mediating cancer malignancy.
- Silencing COX-2 impacts key pathways involved in tumor growth, metastasis, and angiogenesis.
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