| 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
|
| リソース情報 |
| ヒト・動物細胞 |
MCF7(RCB1904) |
