Radiation sensitizing effect of estramustine is not dependent on apoptosis.
BACKGROUND
Estramustine is an anti-mitotic cytostatic drug that also enhances the effect of radiotherapy. The mechanism of radiosensitization is not thoroughly known. Since both radiotherapy and estramustine induce apoptosis in prostate cancer cells, we conducted an experiment to show whether radiosensitization is mediated by apoptosis.


METHODS
DU-145 human prostate cancer cells were xenografted to nude mice and treated with estramustine for 2 weeks and external radiation for 3 to 6 days (18 to 36 Gy). Tumor regression was measured mechanically and the rate of apoptosis defined by the amount of low molecular weight DNA fragmentation. Follow-up time was 1 to 18 days.


RESULTS
The tumor size regressed in the group of mice receiving both radiotherapy and estramustine. Four weeks after the treatment, apoptosis was accentuated in the tumors treated with estramustine or radiation but not with their combination.


CONCLUSIONS
Estramustine potentiates radiotherapy, but not by enhancing radiation-induced apoptosis.
Ståhlberg
Kaarlo
K
Department of Urology, Helsinki University Central Hospital, Helsinki, Finland. kaarlo.stahlberg@hus.fi
Kairemo
Kalevi
K
Erkkilä
Krista
K
Pentikäinen
Virve
V
Sorvari
Pekka
P
Taari
Kimmo
K
Dunkel
Leo
L
Rannikko
Sakari
S
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects; D004961:Estramustine / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D018931:Antineoplastic Agents, Hormonal; D011838:Radiation-Sensitizing Agents; D004961:Estramustine