Targeting castration-induced tumour hypoxia enhances the acute effects of castration therapy in a rat prostate cancer model

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

hypoxia;castration;tirapazamine;prostate;Dunning H

Pathology

Patologi

Pathology

patologi

Publikations- och innehållstyp

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