Anti-proliferative effect of the gastrin-release peptide receptor antagonist RC-3095 plus temozolomide in experimental glioblastoma models.
Malignant gliomas have a dismal prognosis despite multi-modality treatments like neurosurgical resection, radiation therapy and chemotherapy. Evidence has indicated that gastrin-releasing peptide (GRP) and its receptor (GRPR) play a role in the development of a variety of cancers including gliomas. In the present study, we investigated the effects of RC-3095, a selective GRPR antagonist, alone or in combination with temozolomide (TMZ), a DNA alkylating agent, in in vitro and in vivo experimental rat C6 glioma models. Cellular proliferation was significantly reduced by all treatments with the combined administration of TMZ and RC-3095 being the most effective treatment. In in vivo experiments, the control group displayed the largest tumors (52 +/- 15.5 mm(3)), whereas RC-3095 reduced the tumor size, with the most significant effect at the dose of 0.3 mg/kg (21 +/- 9.7 mm(3)). The combined therapy produced further reduction in tumor size (10 +/- 7.5 mm(3)). Our results show that the combination of RC-3095 with TMZ produced an important reduction in in vitro and in vivo glioma growth therefore making RC-3095 a candidate drug to potentiate the effects of the DNA alkylating agent TMZ in the treatment of glioma.
de Oliveira
Marianne Schrader
MS
Academic Hospital Research Center, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, Porto Alegre, RS, Brazil.
Cechim
Giovana
G
Braganhol
Elisandra
E
Santos
Daniel Garcia
DG
Meurer
Luise
L
de Castro
Cláudio Galvão
CG
Brunetto
Algemir Lunardi
AL
Schwartsmann
Gilberto
G
Schwarstmann
Gilberto
G
Battastini
Ana Maria Oliveira
AM
Lenz
Guido
G
Roesler
Rafael
R
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001839:Bombesin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005106:Exploratory Behavior / Q000187:drug effects; D005434:Flow Cytometry; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010446:Peptide Fragments / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors; D000077204:Temozolomide
D000970:Antineoplastic Agents; D010446:Peptide Fragments; D018004:Receptors, Bombesin; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D003606:Dacarbazine; D001839:Bombesin; D000077204:Temozolomide