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Cyclooxygenase-2 in...
Cyclooxygenase-2 inhibition : effects on tumour growth, cell cycling and lymphangiogenesis in a xenograft model of breast cancer
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Barnes, N. L. P. (författare)
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- Wärnberg, Fredrik (författare)
- Uppsala universitet,Endokrinkirurgi
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Farnie, G. (författare)
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White, D. (författare)
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Jiang, W (författare)
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Anderson, E. (författare)
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Bundred, N. J. (författare)
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(creator_code:org_t)
- 2007-02-06
- 2007
- Engelska.
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 96:4, s. 575-582
- Relaterad länk:
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Cyclooxygenase-2 (COX-2) is associated with poor-prognosis breast cancer. We used a nude mouse xenograft model to determine the effects of COX-2 inhibition in breast cancer. Oestrogen receptor (ER)-positive MCF7/HER2-18 and ER-negative MDAMB231 breast cancer cell lines were injected into nude mice and allowed to form tumours. Mice then received either chow containing Celecoxib (a COX-2 inhibitor) or control and tumour growth measured. Tumour proliferation, apoptosis, COX-2, lymphangiogenesis and angiogenesis were assessed by immunohistochemistry (IHC), Western blotting or Q-PCR. Celecoxib inhibited median tumour growth in MCF7/HER2-18 (58.7%, P=0.029) and MDAMB231 (46.3%, P=0.0002) cell lines compared to control. Cyclooxygenase-2 expression decreased following Celecoxib treatment (MCF7/HER2-18 median control 65.3% vs treated 22.5%, P=0.0001). Celecoxib increased apoptosis in MCF7/HER2-18 tumours (TUNEL 0.52% control vs 0.73% treated, P=0.0004) via inactivation of AKT (median pAKT(ser473) 57.3% control vs 35.5% treated, P=0.0001--confirmed at Western blotting). Q-PCR demonstrated decreased podoplanin RNA (lymphangiogenesis marker) in the MCF7/HER2-18 - median 2.9 copies treated vs 66.6 control (P=0.05) and MDAMB231-treated groups--median 160.7 copies vs 0.05 control copies (P=0.015), confirmed at IHC. Cyclooxygenase-2 is associated with high levels of activated AKT(ser473) and lymphangiogenesis in breast cancer. Cyclooxygenase-2 inhibition decreases tumour growth, and may potentially decrease recurrence, by inactivating AKT and decreasing lymphangiogenesis.
Nyckelord
- breast
- cyclooxygenase-2
- apoptosis
- lymphangiogenesis
- MEDICINE
- MEDICIN
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- ref (ämneskategori)
- art (ämneskategori)
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