Dataset Information

Reversed metabolic reprogramming as a measure of cancer treatment efficacy in rat C6 glioma model.

ABSTRACT:

Background

Metabolism in tumor shifts from oxidative phosphorylation to inefficient glycolysis resulting in overproduction of lactate (Warburg effect), and cancers may be effectively treated if this imbalance were corrected. The aim of this longitudinal study of glioblastoma in a rat model was to determine whether the ratio of lactate (surrogate marker for glycolysis) to bicarbonate (for oxidative phosphorylation), as measured via in vivo magnetic resonance imaging of hyperpolarized 13C-labeled pyruvate accurately predicts survival.

Methods

C6 Glioma implanted male Wistar rats (N = 26) were treated with an anti-vascular endothelial growth factor antibody B20.4.1.1 in a preliminary study to assess the efficacy of the drug. In a subsequent longitudinal survival study, magnetic resonance spectroscopic imaging (MRSI) was used to estimate [1-13C]Lactate and [1-13C]Bicarbonate in tumor and contralateral normal appearing brain of glioma implanted rats (N = 13) after injection of hyperpolarized [1-13C]Pyruvate at baseline and 48 hours post-treatment with B20.4.1.1.

Results

A survival of ~25% of B20.4.1.1 treated rats was noted in the preliminary study. In the longitudinal imaging experiment, changes in 13C Lactate, 13C Bicarbonate and tumor size measured at baseline and 48 hours post-treatment did not correlate with survival. 13C Lactate to 13C Bicarbonate ratio increased in all the 6 animals that succumbed to the tumor whereas the ratio decreased in 6 of the 7 animals that survived past the 70-day observation period.

Conclusions

13C Lactate to 13C Bicarbonate ratio (Lac/Bic) at 48 hours post-treatment is highly predictive of survival (p = 0.003). These results suggest a potential role for the 13C Lac/Bic ratio serving as a valuable measure of tumor metabolism and predicting therapeutic response.

SUBMITTER: Datta K

PROVIDER: S-EPMC6907781 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Reversed metabolic reprogramming as a measure of cancer treatment efficacy in rat C6 glioma model.

Datta Keshav K Lauritzen Mette H MH Merchant Milton M Jang Taichang T Liu Shie-Chau SC Hurd Ralph R Recht Lawrence L Spielman Daniel M DM

PloS one 20191212 12

<h4>Background</h4>Metabolism in tumor shifts from oxidative phosphorylation to inefficient glycolysis resulting in overproduction of lactate (Warburg effect), and cancers may be effectively treated if this imbalance were corrected. The aim of this longitudinal study of glioblastoma in a rat model was to determine whether the ratio of lactate (surrogate marker for glycolysis) to bicarbonate (for oxidative phosphorylation), as measured via in vivo magnetic resonance imaging of hyperpolarized 13C- ...[more]

PMID: 31830049

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Project description:BackgroundGlioblastoma multiforme (GBM) is the most malignant brain tumor, with a poor prognosis and life expectancy of 14-16 months after diagnosis. The standard treatment for GBM consists of surgery, radiotherapy, and chemotherapy with temozolomide. Most patients become resistant to treatment after some time, and the tumor recurs. Therefore, there is a need for new drugs to manage GBM. Eslicarbazepine (ESL) is a well-known antiepileptic drug belonging to the dibenzazepine group with anticancer potentials. In this study, for the first time, we evaluated the potential effects of ESL on C6 cell growth, both in vitro and in vivo, and examined its molecular effects.MethodsTo determine the effect of ESL on the c6 cell line, cell viability, proliferation, and migration were evaluated by MTT assay, colony formation, and wound healing assay. Also, apoptosis and cell cycle were examined by flow cytometry, qRT-PCR, and western blotting. In addition, an intracranial model in Wistar rats was used to investigate the effect of ESL in vivo, and the tumor size was measured using both Caliper and MRI.ResultsThe obtained results are extremely consistent and highly encouraging. C6 cell viability, proliferation, and migration were significantly suppressed in ESL-treated C6 cells (p < 0.001), as determined by cell-based assays. ESL treatment led to significant enhancement of apoptosis (p < 0.01), as determined by flow cytometry, and upregulation of genes involved in cell apoptosis, such as the Bax/Bcl2 ratio at RNA (p < 0.05) and protein levels (5.37-fold). Flow cytometric analysis of ESL-treated cells revealed G2/M phase cell cycle arrest. ESL-treated cells demonstrated 2.49-fold upregulation of p21 alongside, 0.22-fold downregulation of cyclin B1, and 0.34-fold downregulation of cyclin-dependent kinase-1 at the protein level. Administration of ESL (30 mg/kg) to male rats bearing C6 intracranial tumors also suppressed the tumor volume and weight (p < 0.01).ConclusionsBased on these novel findings, ESL has the potential for further experimental and clinical studies in glioblastoma.

Dataset Information

Reversed metabolic reprogramming as a measure of cancer treatment efficacy in rat C6 glioma model.

Background

Methods

Results

Conclusions

Publications

Reversed metabolic reprogramming as a measure of cancer treatment efficacy in rat C6 glioma model.

Similar Datasets

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