論文 - 詳細
| RRC ID | 52436 |
|---|---|
| 著者 | Kamata E, Kawamoto T, Ueha T, Hara H, Fukase N, Minoda M, Morishita M, Takemori T, Fujiwara S, Nishida K, Kuroda R, Kurosaka M, Akisue T. |
| タイトル | Synergistic Effects of a Smac Mimetic with Doxorubicin Against Human Osteosarcoma. |
| ジャーナル | Anticancer Res |
| Abstract |
BACKGROUND/AIM:Second mitochondria-derived activator of caspase (Smac) is a proapoptogenic mitochondrial protein that antagonizes inhibitors of apoptosis proteins (IAPs), resulting in induction of apoptosis. In the present study we investigated the effects of a Smac mimetic in combination with doxorubicin against osteosarcoma. MATERIALS AND METHODS:In vitro effects of the combination of a Smac mimetic AT-406 and doxorubicin on cell proliferation and apoptosis in osteosarcoma cell lines were examined using cell proliferation assays, flow cytometry, and immunoblot analyses. For in vivo experiments, human osteosarcoma xenografts were treated with combination of the two substances, and tumor volume and apoptotic activity in treated tumors were assessed. RESULTS:In vitro studies revealed that combination of the two substances significantly inhibited osteosarcoma proliferation with decreased cIAP1 expression and induced apoptosis in osteosarcoma cells. Combination of the two substances significantly suppressed osteosarcoma growth in vivo. Moreover, decreased cIAP1 expression and increased apoptotic activity were observed in tumors treated by their combination of the substances. CONCLUSION:The Smac mimetic AT-406 showed an apoptotic effect and a synergistic antitumor effect with doxorubicin on osteosarcoma. The combination of AT-406 and doxorubicin may serve as a novel therapeutic strategy for osteosarcoma treatment. |
| 巻・号 | 37(11) |
| ページ | 6097-6106 |
| 公開日 | 2017-11-1 |
| DOI | 10.21873/anticanres.12058 |
| PII | 37/11/6097 |
| PMID | 29061790 |
| MeSH | Animals Antibiotics, Antineoplastic / pharmacology Apoptosis / drug effects Azocines / pharmacology* Benzhydryl Compounds / pharmacology* Bone Neoplasms / drug therapy* Bone Neoplasms / metabolism Bone Neoplasms / pathology Cell Proliferation / drug effects Doxorubicin / pharmacology* Drug Synergism* Drug Therapy, Combination Humans Male Mice Mice, Inbred BALB C Mice, Nude Oligopeptides / pharmacology* Osteosarcoma / drug therapy* Osteosarcoma / metabolism Osteosarcoma / pathology Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| IF | 1.994 |
| 引用数 | 7 |
| リソース情報 | |
| ヒト・動物細胞 | MG-63(RCB1890) |