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Sökning: onr:"swepub:oai:DiVA.org:uu-113753" > Cyclooxygenase-2 in...

Cyclooxygenase-2 inhibition : effects on tumour growth, cell cycling and lymphangiogenesis in a xenograft model of breast cancer

Barnes, N. L. P. (författare)
Wärnberg, Fredrik, (författare)
Uppsala universitet, Endokrinkirurgi
Farnie, G. (författare)
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White, D. (författare)
Jiang, W (författare)
Anderson, E. (författare)
Bundred, N. J. (författare)
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2007
Engelska.
Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 96:4, s. 575-582
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • <p>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.</p>

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  (hsv//swe)
MEDICAL AND HEALTH SCIENCES  (hsv//eng)

Nyckelord

breast
cyclooxygenase-2
apoptosis
lymphangiogenesis
MEDICINE
MEDICIN

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