論文 - 詳細
| RRC ID | 63203 |
|---|---|
| 著者 | Gao F, Li M, Yu X, Liu W, Zhou L, Li W. |
| タイトル | Licochalcone A inhibits EGFR signalling and translationally suppresses survivin expression in human cancer cells. |
| ジャーナル | J Cell Mol Med |
| Abstract |
Dysfunction of epidermal growth factor receptor (EGFR) signalling plays a critical role in the oncogenesis of non-small-cell lung cancer (NSCLC). Here, we reported the natural product, licochalcone A, exhibited a profound anti-tumour efficacy through directly targeting EGFR signalling. Licochalcone A inhibited in vitro cell growth, colony formation and in vivo tumour growth of either wild-type (WT) or activating mutation EGFR-expressed NSCLC cells. Licochalcone A bound with L858R single-site mutation, exon 19 deletion, L858R/T790M mutation and WT EGFR ex vivo, and impaired EGFR kinase activity both in vitro and in NSCLC cells. The in silico docking study further indicated that licochalcone A interacted with both WT and mutant EGFRs. Moreover, licochalcone A induced apoptosis and decreased survivin protein robustly in NSCLC cells. Mechanistically, we found that treatment with licochalcone A translationally suppressed survivin through inhibiting EGFR downstream kinases ERK1/2 and Akt. Depletion of the translation initiation complex by eIF4E knockdown effectively inhibited survivin expression. In contrast, knockdown of 4E-BP1 showed the opposite effect and dramatically enhanced survivin protein level. Overall, our data indicate that targeting survivin might be an alternative strategy to sensitize EGFR-targeted therapy. |
| 巻・号 | 25(2) |
| ページ | 813-826 |
| 公開日 | 2021-1-1 |
| DOI | 10.1111/jcmm.16135 |
| PMID | 33247550 |
| PMC | PMC7812290 |
| MeSH | Acrylamides / pharmacology Aniline Compounds / pharmacology Antineoplastic Agents / pharmacology Blotting, Western Carcinoma, Non-Small-Cell Lung / metabolism* Chalcones / pharmacology* ErbB Receptors / genetics ErbB Receptors / metabolism* Exons / genetics Flow Cytometry Humans Immunohistochemistry Mitogen-Activated Protein Kinase 1 / genetics Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / genetics Mitogen-Activated Protein Kinase 3 / metabolism Mutation / genetics Proto-Oncogene Proteins c-akt / genetics Proto-Oncogene Proteins c-akt / metabolism Survivin / genetics Survivin / metabolism Xenograft Model Antitumor Assays |
| IF | 4.486 |
| 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 | |
| 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 | Ba/F3 |