論文 - 詳細
| RRC ID | 69335 |
|---|---|
| 著者 | Watanabe M, Umezawa K, Higashihara M, Horie R. |
| タイトル | Combined inhibition of NF-κB and Bcl-2 triggers synergistic reduction of viability and induces apoptosis in melanoma cells. |
| ジャーナル | Oncol Res |
| Abstract |
Constitutive activation of nuclear factor κB (NF-κB) characterizes melanoma cells. To explore the molecular mechanism of melanoma cell survival by constitutive NF-κB activation, we used the NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ), which directly binds to NF-κB. DHMEQ abrogated constitutive NF-κB activity, which included RelA (p65)/p50 in melanoma cell lines G361 and HMV-II; however, the reduction of the viability was marginal. Expression of c-FLIP was not observed in the melanoma cell lines tested, and DHMEQ could not repress the expression of the Bcl-2 family proteins Bcl-2 and Bcl-xL. Concomitant treatment with DHMEQ and the inhibitor of antiapoptotic Bcl-2 family proteins, GX15-070, triggered synergistic reduction of the viability and induced apoptosis of G361 cells. These results indicate that abrogation of the NF-κB pathway alone is not sufficient to suppress the survival of melanoma cells. The NF-κB and the antiapoptotic Bcl-2 pathways cooperatively support the survival, and the dual targeting triggers synergistic reduction of the viability and induces apoptosis of melanoma cells. |
| 巻・号 | 21(4) |
| ページ | 173-80 |
| 公開日 | 2013-1-1 |
| DOI | 10.3727/096504014X13887748696707 |
| PMID | 24762223 |
| MeSH | Antineoplastic Combined Chemotherapy Protocols / pharmacology* Apoptosis / drug effects Apoptosis / physiology Benzamides / administration & dosage Benzamides / pharmacology* Cell Line, Tumor Cell Survival Cyclohexanones / administration & dosage Cyclohexanones / pharmacology* Drug Synergism Humans Indoles Melanoma / drug therapy* Melanoma / metabolism Melanoma / pathology NF-kappa B / antagonists & inhibitors* NF-kappa B / metabolism Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors* Proto-Oncogene Proteins c-bcl-2 / metabolism Pyrroles / administration & dosage Pyrroles / pharmacology* Signal Transduction / drug effects Tumor Cells, Cultured |
| IF | 4.949 |
| 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HMV-II(RCB0777) |