Inhibition of invasion-associated thromboxane synthase sensitizes experimental gliomas to gamma-radiation.
The invasion- and apoptosis-associated thromboxane synthase gene encoding an enzyme of the arachidonic acid pathway has been implicated in glioma progression. Furegrelate, a specific inhibitor of thromboxane synthase, blocks cell motility, induces apoptosis and increases sensitivity to drug induced apoptosis in human glioma cells in vitro. The impact of furegrelate on the sensitivity of human glioma cells to gamma-irradiation was analyzed using colony formation assay in vitro and an orthotopic mouse model in vivo. Pre-treatment of glioma cells with furegrelate increases radiation sensitivity of cultured glioma cells. Treatment of experimental gliomas with suboptimal doses of radiation and furegrelate results in a significant decrease in tumor volumes compared to untreated controls. Thus, the specific thromboxane synthase inhibitor furegrelate increases death response induced by gamma-radiation in glioma cells in vitro and sensitizes experimental gliomas to radiation treatment in vivo.
Schauff
Anne Katrin
AK
Medical School, University of Luebeck, Ratzeburger Allee 160, Luebeck, Germany.
Kim
Ella L
EL
Leppert
Jan
J
Nadrowitz
Roger
R
Wuestenberg
Robin
R
Brockmann
Mark Alexander
MA
Giese
Alf
A
D000818:Animals; D017849:Animals, Inbred Strains; D001253:Astrocytes / Q000187:drug effects / Q000528:radiation effects; D001572:Benzofurans / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005720:Gamma Rays / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D005910:Glioma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D011836:Radiation Tolerance / Q000187:drug effects* / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013931:Thromboxanes / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection / Q000379:methods
D001572:Benzofurans; D004791:Enzyme Inhibitors; D013931:Thromboxanes; D013930:Thromboxane-A Synthase; C039936:furegrelate