دورية أكاديمية
Enhancement of vincristine sensitivity in retinoblastoma through Janus kinase inhibition by ruxolitinib.
| العنوان: | Enhancement of vincristine sensitivity in retinoblastoma through Janus kinase inhibition by ruxolitinib. |
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| المؤلفون: | Ke F; Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing., Wang N; Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing., Zhang X; Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing., Liu R; Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing., Ren T; Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing., Ke J; Department of Pharmacy., Yang J; Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, China., Yan H; Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing., Ma J; Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing. |
| المصدر: | Anti-cancer drugs [Anticancer Drugs] 2024 Aug 01; Vol. 35 (7), pp. 615-622. Date of Electronic Publication: 2024 May 10. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: England NLM ID: 9100823 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1473-5741 (Electronic) Linking ISSN: 09594973 NLM ISO Abbreviation: Anticancer Drugs Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: London : Lippincott Williams & Wilkins Original Publication: Oxford, UK : Rapid Communications of Oxford, [1990- |
| مواضيع طبية MeSH: | Retinoblastoma*/drug therapy , Retinoblastoma*/pathology , Nitriles*/pharmacology , Pyrimidines*/pharmacology , Vincristine*/pharmacology , Pyrazoles*/pharmacology , Janus Kinase 1*/antagonists & inhibitors , Janus Kinase 1*/metabolism , Drug Resistance, Neoplasm*/drug effects, Animals ; Humans ; Mice ; Janus Kinase 2/antagonists & inhibitors ; Janus Kinase 2/metabolism ; Janus Kinase Inhibitors/pharmacology ; Xenograft Model Antitumor Assays ; Cell Line, Tumor ; Retinal Neoplasms/drug therapy ; Retinal Neoplasms/pathology ; Drug Synergism ; Cell Proliferation/drug effects ; Antineoplastic Combined Chemotherapy Protocols/pharmacology |
| مستخلص: | Chemotherapy remains the main approach conserving vision during the treatment of retinoblastoma, the most prevalent eye cancer in children. Unfortunately, the development of chemoresistance stands as the primary reason for treatment failure. Within this study, we showed that prolonged exposure to vincristine led to heightened expression of JAK1 and JAK2 in retinoblastoma cells, while the other members of the JAK family exhibited no such changes. Employing a genetic intervention, we demonstrated the efficacy of depleting either JAK1 or JAK2 in countering vincristine-resistant retinoblastoma cells. In addition, the dual depletion of both JAK1 and JAK2 produced a more potent inhibitory outcome compared to the depletion of either gene alone. We further demonstrated that ruxolitinib, a small molecular inhibitor of JAK1/2, effectively reduced viability and colony formation in vincristine-resistant retinoblastoma cells. It also acts synergistically with vincristine in retinoblastoma cells regardless of inherent cellular and genetic heterogeneity. The effectiveness of ruxolitinib as standalone treatment against chemoresistant retinoblastoma, as well as its combination with vincristine, was validated in multiple retinoblastoma mouse models. Importantly, mice exhibited favorable tolerance to ruxolitinib administration. We confirmed that the underlying mechanism of ruxolitinib's action in chemoresistant retinoblastoma cells is the inhibition of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling. Our study reveals that the underlying mechanism driving ruxolitinib's impact on chemoresistant retinoblastoma cells is the inhibition of JAK/STAT signaling. This study reveals the contribution of JAK1/2 to the development of chemoresistance in retinoblastoma and underscores the effectiveness of targeting JAK1/2 as a strategy to sensitize retinoblastoma to chemotherapy. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.) |
| References: | Kivela T. The epidemiological challenge of the most frequent eye cancer: retinoblastoma, an issue of birth and death. Br J Ophthalmol 2009; 93:1129–1131. Azimi F, Mirshahi R, Naseripour M. Review: new horizons in retinoblastoma treatment: an updated review article. Mol Vis 2022; 28:130–146. Raval V, Bowen RC, Soto H, Singh A. Intravenous chemotherapy for retinoblastoma in the era of intravitreal chemotherapy: a systematic review. Ocul Oncol Pathol 2021; 7:142–148. Zhang MG, Kuznetsoff JN, Owens DA, Gallo RA, Kalahasty K, Cruz AM, et al. Early mechanisms of chemoresistance in retinoblastoma. Cancers (Basel) 2022; 14:4966. Sun J, Feng D, Xi H, Luo J, Zhou Z, Liu Q, et al. CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy. Mol Oncol 2020; 14:1740–1759. Li C, Zhao J, Sun W. microRNA-222-Mediated VHL downregulation facilitates retinoblastoma chemoresistance by increasing HIF1alpha expression. Invest Ophthalmol Vis Sci 2020; 61:9. Shao F, Pang X, Baeg GH. Targeting the JAK/STAT signaling pathway for breast cancer. Curr Med Chem 2021; 28:5137–5151. Pencik J, Pham HT, Schmoellerl J, Javaheri T, Schlederer M, Culig Z, et al. JAK-STAT signaling in cancer: From cytokines to non-coding genome. Cytokine 2016; 87:26–36. Valle-Mendiola A, Gutierrez-Hoya A, Soto-Cruz I. JAK/STAT signaling and cervical cancer: from the cell surface to the nucleus. Genes (Basel) 2023; 14:1141. Ni Y, Low JT, Silke J, O’Reilly LA. Digesting the role of JAK-STAT and cytokine signaling in oral and gastric cancers. Front Immunol 2022; 13:835997. Agashe RP, Lippman SM, Kurzrock R. JAK. Not just another kinase. Mol Cancer Ther 2022; 21:1757–1764. Bhagwat N, Levine RL, Koppikar P. Sensitivity and resistance of JAK2 inhibitors to myeloproliferative neoplasms. Int J Hematol 2013; 97:695–702. Igelmann S, Neubauer HA, Ferbeyre G. STAT3 and STAT5 activation in solid cancers. Cancers (Basel) 2019; 11:1428. Roskoski R Jr. Janus kinase (JAK) inhibitors in the treatment of neoplastic and inflammatory disorders. Pharmacol Res 2022; 183:106362. Ajayi S, Becker H, Reinhardt H, Engelhardt M, Zeiser R, von Bubnoff N, et al. Ruxolitinib. Recent Results Cancer Res 2018; 212:119–132. Ke F, Yu J, Chen W, Si X, Li X, Yang F, et al. The anti-malarial atovaquone selectively increases chemosensitivity in retinoblastoma via mitochondrial dysfunction-dependent oxidative damage and Akt/AMPK/mTOR inhibition. Biochem Biophys Res Commun 2018; 504:374–379. Busch M, Philippeit C, Weise A, Dunker N. Re-characterization of established human retinoblastoma cell lines. Histochem Cell Biol 2015; 143:325–338. Lu X, Tu H, Tang D, Huang X, Sun F. miR-130a-3p enhances the chemosensitivity of Y79 retinoblastoma cells to vincristine by targeting PAX6 expression. Curr Eye Res 2022; 47:418–425. Zhang H, Li B, Bai SW, Wang HJ. Constitutively active Akt contributes to vincristine resistance in human retinoblastoma cells. Cancer Invest 2010; 28:156–165. Chen B, Lai J, Dai D, Chen R, Li X, Liao N. JAK1 as a prognostic marker and its correlation with immune infiltrates in breast cancer. Aging (Albany NY) 2019; 11:11124–11135. Shen K, Wei Y, Lv T, Song Y, Jiang X, Lu Z, et al. The expression landscape of JAK1 and its potential as a biomarker for prognosis and immune infiltrates in NSCLC. BMC Bioinf 2021; 22:471. Taverna JA, Hung CN, DeArmond DT, Chen M, Lin CL, Osmulski PA, et al. Single-cell proteomic profiling identifies combined AXL and JAK1 inhibition as a novel therapeutic strategy for lung cancer. Cancer Res 2020; 80:1551–1563. Hu X, Li J, Fu M, Zhao X, Wang W. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther 2021; 6:402. Zhang M, Mathews Griner LA, Ju W, Duveau DY, Guha R, Petrus MN, et al. Selective targeting of JAK/STAT signaling is potentiated by Bcl-xL blockade in IL-2-dependent adult T-cell leukemia. Proc Natl Acad Sci U S A 2015; 112:12480–12485. Devos T, Selleslag D, Granacher N, Havelange V, Benghiat FS. Updated recommendations on the use of ruxolitinib for the treatment of myelofibrosis. Hematology 2022; 27:23–31. |
| المشرفين على المادة: | 82S8X8XX8H (ruxolitinib) 0 (Nitriles) 0 (Pyrimidines) 5J49Q6B70F (Vincristine) 0 (Pyrazoles) EC 2.7.10.2 (Janus Kinase 1) EC 2.7.10.2 (Janus Kinase 2) EC 2.7.10.2 (JAK1 protein, human) 0 (Janus Kinase Inhibitors) EC 2.7.10.2 (JAK2 protein, human) |
| تواريخ الأحداث: | Date Created: 20240514 Date Completed: 20240711 Latest Revision: 20240711 |
| رمز التحديث: | 20240712 |
| DOI: | 10.1097/CAD.0000000000001615 |
| PMID: | 38742728 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1473-5741 |
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| DOI: | 10.1097/CAD.0000000000001615 |