論文 - 詳細
| RRC ID | 82880 |
|---|---|
| 著者 | Motoyama M, Shigefuku R, Tanaka N, Nishizawa M, Oshio K, Suhara Y, Yajima I. |
| タイトル | Acyclic Retinoid Inhibits the EGFR/AKT Signaling Pathway and Cancels Cisplatin-resistant Cell Characteristics. |
| ジャーナル | Anticancer Res |
| Abstract |
BACKGROUND/AIM:Lung cancer is among the most prevalent and lethal malignancies worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Overactivation of the EGFR/AKT signaling pathway contributes significantly to NSCLC progression and metastasis. Cisplatin, a widely used chemotherapeutic agent, faces limitations due to severe side effects and the emergence of resistant cancer cells. Acyclic retinoid (ACR), a synthetic derivative of vitamin A, has shown antitumor effects in hepatocellular carcinoma, but its efficacy against NSCLC and cisplatin-resistant cells remains unclear. This study aimed to investigate whether ACR could inhibit EGFR/AKT signaling and enhance therapeutic efficacy against NSCLC and cisplatin-resistant cells. MATERIALS AND METHODS:Human NSCLC A549 cells, cisplatin-resistant A549 (A549CR) cells, and normal lung epithelial BEAS-2B cells were treated with ACR, alone or in combination with cisplatin. Cell viability, apoptosis, and changes in expression/phosphorylation of EGFR, AKT, and cell cycle regulators were assessed using cell viability assay, immunostaining, and immunoblotting. RESULTS:ACR selectively reduced viability of A549 cells with less toxicity to BEAS-2B cells and induced apoptosis via cleaved Caspase-3 activation. ACR inhibited EGFR/AKT signaling and up-regulated p27KIP1 in A549 cells. The combination of ACR and cisplatin synergistically reduced cell viability and suppressed AKT phosphorylation. Notably, ACR also inhibited EGFR/AKT signaling in A549CR cells, restoring sensitivity to cisplatin and reversing EMT-like characteristics. CONCLUSION:ACR effectively inhibits EGFR/AKT signaling and enhances cisplatin sensitivity in NSCLC and cisplatin-resistant cells, suggesting its potential as a promising therapeutic strategy for lung cancer. |
| 巻・号 | 45(2) |
| ページ | 433-443 |
| 公開日 | 2025-2-1 |
| DOI | 10.21873/anticanres.17432 |
| PII | 45/2/433 |
| PMID | 39890166 |
| MeSH | A549 Cells Antineoplastic Agents / pharmacology Apoptosis / drug effects Carcinoma, Non-Small-Cell Lung / drug therapy Carcinoma, Non-Small-Cell Lung / metabolism Carcinoma, Non-Small-Cell Lung / pathology Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects Cisplatin* / pharmacology Drug Resistance, Neoplasm* / drug effects ErbB Receptors* / antagonists & inhibitors ErbB Receptors* / metabolism Humans Lung Neoplasms* / drug therapy Lung Neoplasms* / metabolism Lung Neoplasms* / pathology Proto-Oncogene Proteins c-akt* / metabolism Signal Transduction* / drug effects Tretinoin / analogs & derivatives Tretinoin / pharmacology |
| IF | 1.994 |
| リソース情報 | |
| ヒト・動物細胞 | A549(RCB0098) |