Department of Medical Biosciences, Umeå University, Umeå, Sweden.
BJU Int. 2011 Jun;107(11):1818-24. doi: 10.1111/j.1464-410X.2010.09690.x. Epub 2010 Sep 22.
What's known on the subject? and What does the study add? Castration therapy has rather modest effects on cell death in tumours but can be enhanced by other treatments targeting tumour stroma and vasculature. This study shows that the prostate becomes hypoxic following castration and that targeting hypoxic cells during castration therapy potently enhances the effects of castration.
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.
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.
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.
The present study suggests that castration-induced tumour hypoxia is a novel target for therapy.
探讨去势治疗（晚期前列腺癌的标准治疗方法）与肿瘤缺氧之间的关系，并阐明其对短期和长期治疗反应的重要性。
我们使用雄激素敏感的大鼠 Dunning H 前列腺肿瘤模型，该模型对去势治疗有短暂的反应，随后会复发，与人类患者的情况非常相似。在去势治疗后 1 天和 7 天，使用体视学方法分析完整的肿瘤组织。
去势治疗后，肿瘤组织缺氧短暂上调，并与肿瘤细胞凋亡的诱导相关。当去势治疗与替拉扎明（TPZ）联合使用时，TPZ 是一种靶向缺氧细胞和血管的药物，与单独使用去势或 TPZ 相比，对肿瘤细胞凋亡和肿瘤体积的作用增强。
本研究表明，去势诱导的肿瘤缺氧是一种新的治疗靶点。
