Celecoxib enhances radiation response of secondary bone tumors of a human non-small cell lung cancer via antiangiogenesis in vivo

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Liste des auteurs: Sckell A
Editeur: Springer Verlag (Germany)
Année de publication: 2011
Numéro du volume: 187
Numéro de publication: 1
Page d'accueil: 45
Dernière page: 51
Nombre de pages: 7
ISSN: 0179-7158
Languages: Anglais-Royaume-Uni (EN-GB)


Purpose: : Cyclooxygenase-2 (COX-2) inhibitors mediate a systemic
antitumor activity via antiangiogenesis and seem to enhance the response
of primary tumors to radiation. Radiosensitizing effects of COX-2
inhibition have not been reported for bone metastases. Therefore, the
aim of this study was the investigation of the radiosensitizing effects
of the selective COX-2 inhibitor celecoxib in secondary bone tumors of a
non-small cell lung carcinoma in vivo. Materials and Methods: : Human
A549 lung carcinomas were implanted into a cranial window preparation in
male SCID mice (n = 24). Animals were treated with either celecoxib or
radiation (7 Gy single photon dose) alone or a combination of celecoxib
and radiation, respectively. Untreated animals served as controls. The
impact of radiation and COX-2 inhibition on angiogenesis,
microcirculation, and tumor growth was analyzed over 28 days by means of
intravital microscopy and histological methods. Results: :
Monotherapies with radiation as well as celecoxib had significant
antitumor effects compared to untreated controls. Both therapies reduced
tumor growth and vascularization to a similar extent. The simultaneous
administration of celecoxib and radiation further enhanced the antitumor
and antiangiogenic effects of single-beam radiation. With the combined
treatment approach, tumor vascularization and tumor size were decreased
by 57% and 51%, respectively, as compared to monotherapy with radiation.
Conclusion: : The combined application of radiation therapy and COX-2
inhibition showed synergistic effects concerning the inhibition of tumor
growth and tumor angiogenesis. Therefore, the combination of radiation
with COX-2 inhibitor therapy represents a promising approach to improve
the therapeutic efficacy of radiotherapy of bone metastases. © 2010
Urban & Vogel, Muenchen.


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