title: Anti-proliferative effect of the gastrin-release peptide receptor antagonist RC-3095 plus temozolomide in experimental glioblastoma models.
abstract: 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.
authors.affiliation: Academic Hospital Research Center, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, Porto Alegre, RS, Brazil.
authors.forename: Marianne Schrader
authors.initials: MS
authors.lastname: de Oliveira
authors.forename: Giovana
authors.initials: G
authors.lastname: Cechim
authors.forename: Elisandra
authors.initials: E
authors.lastname: Braganhol
authors.forename: Daniel Garcia
authors.initials: DG
authors.lastname: Santos
authors.forename: Luise
authors.initials: L
authors.lastname: Meurer
authors.forename: Cláudio Galvão
authors.initials: CG
authors.lastname: de Castro
authors.forename: Algemir Lunardi
authors.initials: AL
authors.lastname: Brunetto
authors.forename: Gilberto
authors.initials: G
authors.lastname: Schwartsmann
authors.forename: Gilberto
authors.initials: G
authors.lastname: Schwarstmann
authors.forename: Ana Maria Oliveira
authors.initials: AM
authors.lastname: Battastini
authors.forename: Guido
authors.initials: G
authors.lastname: Lenz
authors.forename: Rafael
authors.initials: R
authors.lastname: Roesler
mesh_terms: 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
chemical_list: 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