Anti-proliferative effect of the gastrin-release peptide receptor antagonist RC-3095 plus temozolomide in experimental glioblastoma models

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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 mm3), whereas RC-3095 reduced the tumor size, with the most significant effect at the dose of 0.3 mg/kg (21 ± 9.7 mm3). The combined therapy produced further reduction in tumor size (10 ± 7.5 mm3). 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.

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