論文 - 詳細
| RRC ID | 86045 |
|---|---|
| 著者 | Liu W, Jiang Z, Wang R, Zhang X, Jiang X, Chen C, Guo P, Yi M, Li W. |
| タイトル | Targeting EGFR-Mcl-1 Axis by Piperlongumine as a Novel Strategy for Non-Small Cell Lung Cancer Therapy. |
| ジャーナル | Am J Chin Med |
| Abstract |
Non-small cell lung cancer (NSCLC) is a malignancy that faces serious resistance challenges in treatment. In this study, we identified Piperlongumine as a promising therapeutic candidate to overcome Osimertinib resistance in NSCLC. We systematically investigated the inhibitory effect of Piperlongumine on NSCLC cells and confirmed that it could effectively inhibit the in vitro kinase activity of wild-type (WT), exon 19 deletion, and L858R/T790M-mutated EGFR. We also found that Piperlongumine-induced intrinsic apoptosis by interfering with the EGFR signaling pathway, which was characterized by the down-regulation of the anti-apoptotic protein Mcl-1. Further mechanistic studies revealed that Piperlongumine-induced degradation of Mcl-1 was dependent on the Akt-GSK3β signaling pathway. Additionally, Piperlongumine-promoted interaction between Mcl-1 and β-TRCP, thereby enhancing β-TRCP-mediated ubiquitination and the degradation of Mcl-1. Furthermore, Piperlongumine significantly inhibited tumor growth in both Osimertinib-sensitive and resistant NSCLC xenograft models. These findings highlight the potential of Piperlongumine as an effective agent in overcoming EGFR-targeted therapy resistance and suggest new avenues for its clinical application in NSCLC treatment. |
| 巻・号 | 53(2) |
| ページ | 597-619 |
| 公開日 | 2025-1-1 |
| DOI | 10.1142/S0192415X25500235 |
| PMID | 40145280 |
| MeSH | Acrylamides / pharmacology Aniline Compounds / pharmacology Animals Apoptosis / drug effects Apoptosis / genetics Carcinoma, Non-Small-Cell Lung* / drug therapy Carcinoma, Non-Small-Cell Lung* / genetics Carcinoma, Non-Small-Cell Lung* / metabolism Carcinoma, Non-Small-Cell Lung* / pathology Cell Line, Tumor Dioxolanes* / pharmacology Dioxolanes* / therapeutic use Drug Resistance, Neoplasm / drug effects Drug Resistance, Neoplasm / genetics ErbB Receptors* / genetics ErbB Receptors* / metabolism Humans Indoles Lung Neoplasms* / drug therapy Lung Neoplasms* / genetics Lung Neoplasms* / metabolism Lung Neoplasms* / pathology Mice Mice, Nude Myeloid Cell Leukemia Sequence 1 Protein* / genetics Myeloid Cell Leukemia Sequence 1 Protein* / metabolism Phytotherapy* Piperidones Pyrimidines Signal Transduction* / drug effects Signal Transduction* / genetics Xenograft Model Antitumor Assays |
| IF | 3.682 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | |
| 各媒体での言及数の合計 | 3 |
| 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 |