Ketamine suppresses the proliferation of rat C6 glioma cells

Niwa,Hidetomo; Furukawa,Ken‑Ichi; Seya,Kazuhiko; Hirota,Kazuyoshi

doi:10.3892/ol.2017.6806

October-2017 Volume 14 Issue 4

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October-2017 Volume 14 Issue 4

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Article

Ketamine suppresses the proliferation of rat C6 glioma cells

Authors:
- Hidetomo Niwa
- Ken‑Ichi Furukawa
- Kazuhiko Seya
- Kazuyoshi Hirota
View Affiliations / Copyright

Affiliations: Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036‑8562, Japan, Department of Pharmacology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036‑8562, Japan
Pages: 4911-4917
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Published online on: August 24, 2017

https://doi.org/10.3892/ol.2017.6806
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Abstract

The present study investigated the effects of N‑methyl‑D‑aspartate receptor (NMDAR) antagonist ketamine, on the growth of gliomas. To analyze the effects of ketamine treatment, rat C6 glioma cells arising from astrocytes, and RNB cells representing non‑malignant astrocytes, were examined. In ketamine‑treated C6 cells, the gene expression changes associated with cell proliferation following ketamine treatment were evaluated using a cDNA microarray. A cell proliferation assay was performed to analyze the dose‑dependent proliferation of C6 glioma and RNB cells following culture (72 h) with ketamine treatment (0‑100 µM). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed following cell incubation with/without ketamine, to confirm if the ketamine‑induced cell death of C6 glioma and RNB cells were due to apoptosis. In addition, cell proliferation and TUNEL assays were performed following cell incubations with a selective NMDAR antagonist, D‑2‑amino‑5‑phosphonovaleric acid (D‑AP5). Analysis of the cDNA microarray indicated that the growth of C6 glioma cells were suppressed by the effects of ketamine. Furthermore, results of the proliferation assay confirmed that ketamine treatment inhibited C6 cell proliferation, most notably at a dose of 30 µM (n=7, 66.4%; P<0.001). The TUNEL assay results revealed that ketamine induced an apoptotic effect on C6 glioma cells, with a significant effect on the rate of death observed at all tested concentrations (3, 10, 30 and 100 µM). Results of the aforementioned proliferation and TUNEL assay experiments were reproduced when ketamine was replaced with a selective NMDAR antagonist, D‑AP5. However, the NMDAR antagonist‑induced effects were not observed in RNB cell cultures. Although it would be premature to apply the results from the present study to human cases, these results indicated that ketamine is an anesthetic candidate providing potential benefit for glioma resection.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Ketamine suppresses the proliferation of rat C6 glioma cells

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