Targeting castration-induced tumour hypoxia enhances the acute effects of castration therapy in a rat prostate cancer model
2011 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 107, no 11, 1818-1824 p.Article in journal (Refereed) Published
OBJECTIVE: • To explore the effects of castration therapy, the standard treatment for advanced prostate cancer, in relation to tumour hypoxia and to elicit its importance for the short- and long-term therapeutic response.
MATERIAL AND METHODS: • We used the androgen-sensitive rat Dunning H prostate tumour model that transiently responds to castration treatment followed by a subsequent relapse, much like the scenario in human patients. • Tumour tissues were analysed using stereological methods in intact, 1 and 7 days after castration therapy.
RESULTS: • Hypoxia was transiently up-regulated after castration therapy and correlated with the induction of tumour cell apoptosis. • When castration therapy was combined with tirapazamine (TPZ), a drug that targets hypoxic cells and the vasculature, the effects on tumour cell apoptosis and tumour volume were enhanced in comparison to either castration or TPZ alone.
CONCLUSION: • The present study suggests that castration-induced tumour hypoxia is a novel target for therapy.
Place, publisher, year, edition, pages
2011. Vol. 107, no 11, 1818-1824 p.
Cell and Molecular Biology
Research subject Pathology
IdentifiersURN: urn:nbn:se:umu:diva-40758DOI: 10.1111/j.1464-410X.2010.09690.xPubMedID: 20860653OAI: oai:DiVA.org:umu-40758DiVA: diva2:402662