論文 - 詳細
| RRC ID | 62242 |
|---|---|
| 著者 | Yazama H, Kitatani K, Fujiwara K, Kato M, Hashimoto-Nishimura M, Kawamoto K, Hasegawa K, Kitano H, Bielawska A, Bielawski J, Okazaki T. |
| タイトル | Dietary glucosylceramides suppress tumor growth in a mouse xenograft model of head and neck squamous cell carcinoma by the inhibition of angiogenesis through an increase in ceramide. |
| ジャーナル | Int J Clin Oncol |
| Abstract |
BACKGROUND:We previously reported that dietary glucosylceramides show cancer-prevention activity in a mouse xenograft model of human head and neck cancer cells (SCCKN). However, the mechanism was unclear. Ceramides, metabolites of glucosylceramides, induce apoptotic cell death in various malignancies. Here, we investigated the inhibitory effects of dietary glucosylceramides on tumor growth in vivo and in vitro. METHODS:SCCKN were subcutaneously inoculated into the right flanks of NOD/SCID mice. Mice were treated with or without dietary glucosylceramides (300 mg/kg) daily for 14 consecutive days after confirmation of tumor progression. Microvessel areas around the tumor were assessed by hematoxylin-eosin staining and immunohistochemistry of CD31, and, as markers for angiogenesis, protein levels of VEGF, VEGF receptor-2, and HIF-1α were assessed by Western blotting. Mass spectrometry was performed to measure the levels of sphingolipids in mouse serum after treatment with dietary glucosylceramides. RESULTS:Oral administration of glucosylceramides significantly decreased SCCKN growth in the xenograft model with inhibition of angioinvasion. In tumor-invasive areas, VEGF and HIF-1α in the tumor cells, and VEGF receptor-2 in endothelial cells decreased after treatment with dietary glucosylceramides. Dietary glucosylceramides increased serum levels of sphingosine-based ceramides as compared to the control. In SCCKN and UV♀2 cells, C6-ceramide suppressed the expressions of VEGF, VEGF receptor-2, and HIF-1α in vitro. CONCLUSION:These results suggest that dietary glucosylceramides trigger the de novo pathway of ceramide synthesis, indicating that sphingosine-based ceramide suppresses the growth of head and neck tumors through the inhibition of pro-angiogenic signals such as VEGF, VEGF receptor-2, and HIF-1α. |
| 巻・号 | 20(3) |
| ページ | 438-46 |
| 公開日 | 2015-6-1 |
| DOI | 10.1007/s10147-014-0734-y |
| PMID | 25080062 |
| MeSH | Administration, Oral Angiogenesis Inhibitors / administration & dosage* Animals Carcinoma, Squamous Cell / diet therapy* Carcinoma, Squamous Cell / metabolism Ceramides / biosynthesis Glucosylceramides / administration & dosage* Head and Neck Neoplasms / diet therapy* Head and Neck Neoplasms / metabolism Humans Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis Mice Mice, Inbred NOD Mice, SCID Neovascularization, Pathologic / diet therapy* Neovascularization, Pathologic / metabolism Vascular Endothelial Growth Factor A / biosynthesis Vascular Endothelial Growth Factor Receptor-2 / biosynthesis Xenograft Model Antitumor Assays |
| IF | 2.879 |
| リソース情報 | |
| ヒト・動物細胞 | SCCKN(RCB0441) UV♀2(RCB1994) |