論文 - 詳細
| RRC ID | 43908 |
|---|---|
| 著者 | Dateoka S, Ohnishi Y, Kakudo K. |
| タイトル | Effects of CRM197, a specific inhibitor of HB-EGF, in oral cancer. |
| ジャーナル | Med Mol Morphol |
| Abstract |
CRM197, a nontoxic mutant of diphtheria toxin, is a specific inhibitor of heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), which belongs to the EGF family that has been implicated in the increased progression, proliferation, and metastasis of oral cancer. In this study, we analyzed the antitumor effects of CRM197, which represent possible chemotherapeutic agents for oral cancer. In the experiment, we used the oral squamous cell carcinoma cell lines HSC3 and SAS. Cells treated with CRM197 were analyzed based on cell viability, MTT assay, invasion assay, Western blot, and zymography. HSC3 cells were injected subcutaneously into female BALB/c nu/nu mice at 5 weeks of age. CRM197 and/or CDDP were injected intraperitoneally into tumor-bearing mice, and tumor volume was measured over time. HB-EGF expression in HSC3 and SAS cells treated with CRM197 was significantly reduced and cell proliferation was inhibited. The invasiveness of CRM197-treated cells was relatively low. MMP-9 and VEGF were suppressed in HSC3 treated with CRM197 on zymography and Western blot. Further, tumor growth in xenografted mice was suppressed by CRM197 or CDDP at 1 mg/kg/day. Also, the coadministration of CDDP and CRM197 at 1 mg/kg/day completely inhibited tumor formation. These results suggest that HB-EGF is a target for oral cancer and that CRM197 is effective in oral cancer therapy. |
| 巻・号 | 45(2) |
| ページ | 91-7 |
| 公開日 | 2012-6-1 |
| DOI | 10.1007/s00795-011-0543-6 |
| PMID | 22718294 |
| MeSH | Animals Antineoplastic Agents / administration & dosage Antineoplastic Agents / pharmacology Antineoplastic Combined Chemotherapy Protocols / therapeutic use Apoptosis / drug effects Bacterial Proteins / administration & dosage Bacterial Proteins / pharmacology* Blotting, Western Carcinoma, Squamous Cell / drug therapy* Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects Cisplatin / administration & dosage Cisplatin / pharmacology Dose-Response Relationship, Drug Female Gene Expression Regulation, Neoplastic / drug effects Heparin-binding EGF-like Growth Factor Humans Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism* Matrix Metalloproteinase 9 / metabolism Mice Mice, Inbred BALB C Mice, Nude Mouth Neoplasms / drug therapy* Mouth Neoplasms / metabolism Mouth Neoplasms / pathology Reverse Transcriptase Polymerase Chain Reaction Tumor Burden / drug effects Vascular Endothelial Growth Factor A / metabolism Xenograft Model Antitumor Assays |
| IF | 2.429 |
| 引用数 | 18 |
| WOS 分野 | MICROSCOPY BIOLOGY PATHOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | SAS(RCB1974) |