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Anti-proliferative effect of the gastrin-release peptide receptor antagonist RC-3095 plus temozolomide in
Marianne Schrader de Oliveira1, Giovana Cechim, Elisandra Braganhol
1Academic Hospital Research Center, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, Porto Alegre, RS, Brazil.
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.
Insights
This study shows that combining RC-3095, a gastrin-releasing peptide receptor antagonist, with temozolomide (TMZ) significantly inhibits glioma growth in both lab and animal models, offering a promising new treatment strategy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Malignant gliomas have a poor prognosis despite standard treatments.
- Gastrin-releasing peptide (GRP) and its receptor (GRPR) are implicated in glioma development.
Purpose of the Study:
- To investigate the efficacy of a selective GRPR antagonist, RC-3095, alone and with temozolomide (TMZ) in rat C6 glioma models.
- To evaluate the combined effect of RC-3095 and TMZ on glioma cell proliferation and tumor growth.
Main Methods:
- In vitro and in vivo experiments using rat C6 glioma models.
- Administration of RC-3095, TMZ, or a combination of both.
- Assessment of cellular proliferation and tumor volume.
Main Results:
- Both RC-3095 and TMZ individually reduced glioma cell proliferation and tumor growth.
- The combination of RC-3095 and TMZ demonstrated the most significant reduction in both in vitro and in vivo glioma growth.
- RC-3095 at 0.3 mg/kg significantly reduced tumor size in vivo.
Conclusions:
- RC-3095 potentiates the anti-glioma effects of TMZ.
- The combination therapy of RC-3095 and TMZ is a promising strategy for glioma treatment.
- RC-3095 is a potential candidate drug to enhance TMZ efficacy in glioma therapy.
