Radiosensitizing effect of estramustine in malignant glioma in vitro and in vivo.
Estramustine-phosphate (EMP), a combination of nornitrogen mustard and 17 beta-estradiol, has been demonstrated to exert specific antiproliferative effects on human glioma cells in vitro. The cytotoxic effect is, at least partially, mediated by inhibiting microtubule function. In this study the combined effect of EMP and radiation was evaluated in the human glioma cell-lines, 251-MG and 105-MG, in vitro, and in the rat glioma BT4C in vitro and in vivo. In all cell-lines an additive effect of EMP and radiation was obtained in vitro. Assuming equal effect of EMP is obtained in subsequent radiation fractions, the cell kill will be increased from 2-3 to 5-10 logs if delivering 30 fractions of 2 Gy combined with EMP. In the BT4C rat model the combined effect was found to be synergistic. Flow cytometry demonstrated an arrest in G2/M phase in all cell-lines after EMP treatment. This block in G2/M phase in addition to the previously demonstrated induction of free oxygen radicals, and the increase of blood flow with an assumed subsequent increase of oxygenation, might provide an explanation for the observed radiosensitizing effect of estramustine.
Bergenheim
A T
AT
Department of Oncology, University Hospital, Umeå, Sweden.
Zackrisson
B
B
Elfverson
J
J
Roos
G
G
Henriksson
R
R
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004961:Estramustine / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005910:Glioma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D011838:Radiation-Sensitizing Agents; D004961:Estramustine