دورية أكاديمية
Pharmacological drug screening to inhibit uveal melanoma metastatic cells either via EGF-R, MAPK, mTOR or PI3K.
| العنوان: | Pharmacological drug screening to inhibit uveal melanoma metastatic cells either via EGF-R, MAPK, mTOR or PI3K. |
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| المؤلفون: | Kassumeh S; Department of Ophthalmology, University Hospital, LMU Munich, Munich 80336, Germany., Arrow S; Department of Ophthalmology, University Hospital, University Ulm, Ulm 89075, Germany., Kafka A; Department of Ophthalmology, University Hospital, LMU Munich, Munich 80336, Germany., Luft N; Department of Ophthalmology, University Hospital, LMU Munich, Munich 80336, Germany., Priglinger SG; Department of Ophthalmology, University Hospital, LMU Munich, Munich 80336, Germany., Wolf A; Department of Ophthalmology, University Hospital, University Ulm, Ulm 89075, Germany., Eibl-Lindner K; Department of Ophthalmology, University Hospital, LMU Munich, Munich 80336, Germany., Wertheimer CM; Department of Ophthalmology, University Hospital, University Ulm, Ulm 89075, Germany. |
| المصدر: | International journal of ophthalmology [Int J Ophthalmol] 2022 Oct 18; Vol. 15 (10), pp. 1569-1576. Date of Electronic Publication: 2022 Oct 18 (Print Publication: 2022). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Press of International Journal of Ophthalmology Country of Publication: China NLM ID: 101553860 Publication Model: eCollection Cited Medium: Print ISSN: 2222-3959 (Print) Linking ISSN: 22223959 NLM ISO Abbreviation: Int J Ophthalmol Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Xi'an, China : Press of International Journal of Ophthalmology |
| مستخلص: | Aim: To screen five potential pharmacological substances specifically targeting EGF-R, MAPK, mTOR, or PI3K for their antiproliferative effects, possible impact on cell viability, as well as cell death rates on three different uveal melanoma metastasis cell lines in vitro . Methods: Three different uveal melanoma metastasis cell lines (OMM2.5, OMM2.3, and OMM1), that originated from human hepatic and subcutaneous metastasis, were exposed to inhibitors of different targets: erlotinib (EGF-R), everolimus (mTOR), selumetinib (MAPK), trametinib (MAPK) or the alkylphosphocholine erufosine (PI3K). Cell viability was assessed with a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) dye reduction assay after 24h of treatment. Antiproliferative effects were evaluated separately after a 72-hour incubation of the cells with the pharmacological substance. Subsequently, the IC Results: Selumetinib, trametinib, and erufosine significantly decreased cell viability of all OMM cell lines ( P <0.04). In addition, selumetinib and trametinib showed a significant inhibition of cell proliferation ( P <0.05). Everolimus and erlotinib solely inhibited cell proliferation at the used concentrations ( P <0.05). Besides an increase of necrotic cells after erufosine treatment ( P <0.001), no changes in the number of dead cells for the other substances were observed. Conclusion: The preliminary drug screening demonstrates five new candidates, successfully targeting the canonical MAPK/ERK and PI3K/AKT/mTOR pathways in uveal melanoma metastasis cells in vitro . Hence, these findings provide an experimental basis to explore future single or combined therapy strategies for metastatic uveal melanoma. (International Journal of Ophthalmology Press.) |
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| فهرسة مساهمة: | Keywords: erlotinib; erufosine; selumetinib; trametinib; uveal melanoma |
| تواريخ الأحداث: | Date Created: 20221020 Latest Revision: 20221021 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9522573 |
| DOI: | 10.18240/ijo.2022.10.02 |
| PMID: | 36262851 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2222-3959 |
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| DOI: | 10.18240/ijo.2022.10.02 |