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Journal of Cancer Research and Clinical Oncology

Published in:

01-02-2014 | Original Paper

Concomitant treatment with pertussis toxin plus temozolomide increases the survival of rats bearing intracerebral RG2 glioma

Authors: Roxana Magaña-Maldonado, Karen Manoutcharian, Norma Y. Hernández-Pedro, Edgar Rangel-López, Verónica Pérez-De la Cruz, César Rodríguez-Balderas, Julio Sotelo, Benjamín Pineda

Published in: Journal of Cancer Research and Clinical Oncology | Issue 2/2014

Abstract

Purpose

Glioblastoma multiforme is the most frequent primary brain tumor, it has poor prognosis, and it remains refractory to current treatment. The success of temozolomide (TMZ) appears to be limited by the occurrence of chemoresistance. Recently, we report the use of pertussis toxin as adjuvant immunotherapy in a C6 glioma model; showing a decrease in tumoral size, it induced selective cell death in Treg cells, and it elicited less infiltration of tumoral macrophages. Here, we evaluated the cytotoxic effect of pertussis toxin in combination with TMZ for glioma treatment, both in vitro and in vivo RG2 glioma model.

Methods

We determined cell viability, cell cycle, apoptosis, and autophagy on treated RG2 cells through flow cytometry, immunofluorescence, and Western blot assays. Twenty-eight rats were divided in four groups (n = 7) for each treatment. After intracranial implantation of RG2 cells, animals were treated with TMZ (10 mg/Kg/200 μl of apple juice), PTx (2 μg/200 μl of saline solution), and TMZ + PTx. Animals without treatment were considered as control.

Results

We found an induction of apoptosis in around 20 % of RG2 cells, in both single treatments and in their combination. Also, we determined the presence of autophagy vesicles, without any modifications in the cell cycle in the TMZ – PTx-treated groups. The survival analyses showed an increase due to individual treatments; while in the group treated with the combination TMZ − PTx, this effect was enhanced.

Conclusion

We show that the concomitant use of pertussis toxin plus TMZ could represent an advantage to improve the glioma treatment.

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Title: Concomitant treatment with pertussis toxin plus temozolomide increases the survival of rats bearing intracerebral RG2 glioma
Authors: Roxana Magaña-Maldonado
Karen Manoutcharian
Norma Y. Hernández-Pedro
Edgar Rangel-López
Verónica Pérez-De la Cruz
César Rodríguez-Balderas
Julio Sotelo
Benjamín Pineda
Publication date: 01-02-2014
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 2/2014
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-013-1565-3

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