論文 - 詳細
| RRC ID | 67415 |
|---|---|
| 著者 | Kan S, Koido S, Okamoto M, Hayashi K, Ito M, Kamata Y, Komita H, Ishidao T, Nagasaki E, Homma S. |
| タイトル | Gemcitabine treatment enhances HER2 expression in low HER2-expressing breast cancer cells and enhances the antitumor effects of trastuzumab emtansine. |
| ジャーナル | Oncol Rep |
| Abstract |
Trastuzumab emtansine (T-DM1), trastuzumab-conjugated with a cytotoxic agent, has shown promising antitumor effects in breast cancer. Since a good therapeutic response using T-DM1 treatment requires high human epidermal growth factor receptor 2 (HER2) expression, breast cancers with low or no HER2 expression have not been used for T-DM1 treatment. The aim of the present study was to show that treatment of low HER2-expressing breast cancer cells with gemcitabine (GEM) enhanced HER2 expression using RT-qPCR, immunoblot and flow cytometric analysis. The results showed that GEM treatment significantly enhanced HER2 expression in MDA-MB-231, MCF7 and BT-20 breast cancer cells, while paclitaxel (PTX) treatment induced lower or no enhancement in HER2 expression. The expression of HER2 mRNA was also enhanced in GEM-treated MCF7 cells. Treatment with an inhibitor for nuclear factor-(NF)-κB suppressed GEM-induced HER2 upregulation, indicating that NF-κB activation by GEM may be associated with HER2 upregulation. T-DM1 binding to HER2 on MCF-7 cells was enhanced by GEM pretreatment and the combined treatment of GEM and T-DM1 synergistically inhibited the proliferation of MCF7 cells. Thus, the combined treatment with GEM and T-DM1 may be a promising therapeutic modality for low HER2-expressing breast cancers, which was facilitated by the unique HER2-upregulating effect of GEM. |
| 巻・号 | 34(1) |
| ページ | 504-10 |
| 公開日 | 2015-7-1 |
| DOI | 10.3892/or.2015.3974 |
| PMID | 25976081 |
| MeSH | Ado-Trastuzumab Emtansine Antibodies, Monoclonal, Humanized / pharmacology* Antineoplastic Agents / pharmacology* Breast Neoplasms / drug therapy* Breast Neoplasms / genetics Breast Neoplasms / metabolism Cell Line, Tumor Cell Proliferation / drug effects Deoxycytidine / analogs & derivatives* Deoxycytidine / pharmacology Drug Synergism Female Gemcitabine Humans MCF-7 Cells Maytansine / analogs & derivatives* Maytansine / pharmacology Paclitaxel / pharmacology Receptor, ErbB-2 / genetics* Receptor, ErbB-2 / metabolism Trastuzumab Up-Regulation* |
| IF | 3.417 |
| 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 |
| リソース情報 | |
| ヒト・動物細胞 | MCF7(RCB1904) |