Potentiation of antiglioma effect with combined temozolomide and interferon-beta.
Temozolomide (TMZ) is a DNA methylating agent that has shown promising antitumor activity against high grade glioma. Interferon-beta (IFN-beta) is known to have antiproliferative and antiangiogenic activities. The aim of this study was to elucidate whether an antiglioma effect could be potentiated by the combination of TMZ and IFN-beta. In vitro, the combination of these drugs suppressed the proliferative and migratory activities, as well as enhance of the apoptosis and cell cycle (S phase) arrest of U-87 cells more efficiently than TMZ or IFN-beta alone. IFN-beta exerted a potent inhibitory effect on the proliferation of human umbilical vein endothelial cells (HUVEC); however, no additive or synergistic effect was observed with the addition of TMZ. To determine in vivo effect, nude mice bearing intracerebral U-87 xenograft inoculation were treated with intraperitoneal administration of PBS, TMZ (15 mg/kg for 3 days), IFN-beta (2x10(5) IU for 15 days), and a TMZ + IFN-beta combination. The combined treatment (median 62.0+/-8.6 days, P=0.0005) was observed to significantly increase the survival of the animals compared to treatment with PBS (median 30.0+/-2.5 days), TMZ (median 41.0+/-3.5 days) or IFN-beta (mean 36.0+/-2.5 days). These results suggest that antiglioma activity can be enhanced by the combination of TMZ and IFN-beta, providing the possibility for a new strategy development in the management of malignant glioma.
Park
Jin-A
JA
Department of Neurosurgery, The Catholic University of Korea, Seoul 137-701, Korea.
Joe
Young-Ae
YA
Kim
Tai-Gyu
TG
Hong
Yong-Kil
YK
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004357:Drug Synergism; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D000077204:Temozolomide
D016899:Interferon-beta; D003606:Dacarbazine; D000077204:Temozolomide