Castration Therapy of Prostate Cancer Results in Downregulation of HIF-1{alpha} Levels

Journal Article · Thu Mar 01 04:00:00 EST 2012 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2011.10.038· OSTI ID:22056124

Al-Ubaidi, Firas L.T. ^[1]; Schultz, Niklas ^[1]; Egevad, Lars ^[2]; Granfors, Torvald ^[3]; Helleday, Thomas ^[1]

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1. Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm (Sweden)
2. Department of Oncology-Pathology, Karolinska Institutet, Stockholm (Sweden)
3. Department of Urology, Central Hospital, Vaesteras (Sweden)

Background and Purpose: Neoadjuvant androgen deprivation in combination with radiotherapy of prostate cancer is used to improve radioresponsiveness and local tumor control. Currently, the underlying mechanism is not well understood. Because hypoxia causes resistance to radiotherapy, we wanted to test whether castration affects the degree of hypoxia in prostate cancer. Methods and Materials: In 14 patients with locally advanced prostate cancer, six to 12 prostatic needle core biopsy specimens were taken prior to castration therapy. Bilateral orchidectomy was performed in 7 patients, and 7 were treated with a GnRH-agonist (leuprorelin). After castrationm two to four prostatic core biopsy specimens were taken, and the level of hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) in cancer was determined by immunofluorescence. Results: Among biopsy specimens taken before castration, strong HIF-1{alpha} expression (mean intensity above 30) was shown in 5 patients, weak expression (mean intensity 10-30) in 3 patients, and background levels of HIF-1{alpha} (mean intensity 0-10) in 6 patients. Downregulation of HIF-1{alpha} expression after castration was observed in all 5 patients with strong HIF-1{alpha} precastration expression. HIF-1{alpha} expression was also reduced in 2 of 3 patients with weak HIF-1{alpha} precastration expression. Conclusions: Our data suggest that neoadjuvant castration decreases tumor cell hypoxia in prostate cancer, which may explain increased radiosensitivity after castration.

• OSTI ID: 22056124
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 3 Vol. 82; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
ANDROGENS
ANOXIA
BIOPSY
CASTRATION
NEOPLASMS
PATIENTS
PROSTATE
RADIOSENSITIVITY
RADIOTHERAPY
TUMOR CELLS