Impact of trehalose and hydroxychloroquine on the function of BRAF (V600E)-siRNA in the A375 melanoma cells | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 4، دوره 28، شماره 11، بهمن 2025، صفحه 1486-1494 اصل مقاله (511.79 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2025.85017.18394 | ||
| نویسندگان | ||
| Elmira Toobchi1؛ Rana Moradian Tehrani* 2؛ Mohammadreza Sharifi3؛ Fatemeh Tabandeh4؛ Negin Hadisadegh5 | ||
| 1Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran | ||
| 2Department of Genetics and Molecular Sciences, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran | ||
| 3Department of Genetics and Molecular biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran | ||
| 4Department of Genetics and Molecular biology, Faculty of Medicine, Isfahan university of Medical Sciences, Isfahan, Iran | ||
| 5Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran | ||
| چکیده | ||
| Objective(s): Melanoma, a lethal form of skin cancer, is closely linked to mutations in melanocytes. Due to increased resistance to chemotherapy, innovative strategies, including gene and combination therapies, are being explored. This study evaluates the effects of trehalose (TRE) and hydroxychloroquine (HCQ) in enhancing the efficacy of BRAF (V600E)-siRNA in A375 cells. Materials and Methods: The A375 cells were treated, and changes in cell viability were assessed using MTT assays. Apoptosis was evaluated using flow cytometry. Additionally, gene expression analysis of B-Raf proto-oncogene, serine/threonine kinase (BRAF), Caspase 3 (CASP3), and Phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) was performed using quantitative RT-PCR. Results: HCQ treatment reduced cell viability and increased apoptosis compared to both control cells and cells treated with TRE. Gene expression analysis showed a significant down-regulation of BRAF expression in cells treated with HCQ and BRAF (V600E)-siRNA compared to siRNA-only treated cells. CASP3 expression was significantly up-regulated in cells treated with combined HCQ and siRNA, indicating a stronger apoptotic response. PIK3R3 expression showed no significant change in the transfected groups. Conclusion: TRE, either alone or combined with siRNA, showed limited efficacy and may counteract the apoptotic benefits of HCQ. Conversely, HCQ, whether used alone or in combination with siRNA, enhanced apoptosis, suggesting promise as a potential treatment for melanoma. | ||
| کلیدواژهها | ||
| BRAF (V600E)؛ Hydroxychloroquine؛ Melanoma؛ siRNA؛ Trehalose | ||
| مراجع | ||
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