論文 - 詳細
| RRC ID | 52390 |
|---|---|
| 著者 | Haryu S, Saito R, Jia W, Shoji T, Mano Y, Sato A, Kanamori M, Sonoda Y, Sampetrean O, Saya H, Tominaga T. |
| タイトル | Convection-enhanced delivery of sulfasalazine prolongs survival in a glioma stem cell brain tumor model. |
| ジャーナル | J Neurooncol |
| Abstract |
Expression of CD44 in glioma cells was previously correlated with tumor grade and is considered a stem cell marker. CD44 stabilizes the cystine-glutamate transporter (xCT) and inhibits apoptosis in cancer stem cells (CSCs). Recently it was found that Sulfasalazine (SSZ), an anti-inflammatory drug, acts as an inhibitor of xCT and therefore has potential as a targeted therapy for CSCs. In this study, we tested an efficacy of SSZ against glioma stem cell model developed in rats. As poor penetration of blood-brain barrier resulted in insufficient efficacy of systemic SSZ treatment, SSZ was delivered locally with convection-enhanced delivery (CED). In vitro, expression of CD44 in glioma cells and efficacy of SSZ against glioma cells and glioma stem cells were confirmed. SSZ demonstrated anti-proliferative activity in a dose dependent manner against these cells. This activity was partially reversible with the addition of antioxidant, N-acetyl-L-cysteine, to the medium. In vivo, CED successfully delivered SSZ into the rat brain parenchyma. When delivered at 5 mM concentration, which was the highest possible concentration when SSZ was dissolved in water, CED of SSZ resulted in almost no tissue damage. Against highly malignant bRiTs-G3 brain tumor xenografted rat model; the glioma stem cell model, CED of SSZ at 5 mM concentration induced apoptosis and prolonged survival. Consequently, CED of SSZ induced glioma stem cell death without evidence of tissue damage to normal brain parenchyma. This strategy may be a promising targeted treatment against glioma stem cells. |
| 巻・号 | 136(1) |
| ページ | 23-31 |
| 公開日 | 2018-1-1 |
| DOI | 10.1007/s11060-017-2621-7 |
| PII | 10.1007/s11060-017-2621-7 |
| PMID | 28929335 |
| MeSH | Animals Anti-Inflammatory Agents, Non-Steroidal / administration & dosage Antineoplastic Agents / administration & dosage* Apoptosis / drug effects Brain Chemistry Brain Neoplasms / drug therapy* Brain Neoplasms / metabolism Cell Line, Tumor Cell Proliferation / drug effects Convection Disease Models, Animal Drug Delivery Systems Glioma / drug therapy* Glioma / metabolism Humans Hyaluronan Receptors / metabolism Male Mice Neoplastic Stem Cells / drug effects Rats Sulfasalazine / administration & dosage* Survival Analysis Xenograft Model Antitumor Assays |
| IF | 3.06 |
| 引用数 | 4 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | A172(RCB2530) |