Pharmacological drug screening to inhibit uveal melanoma metastatic cells either via EGF-R, MAPK, mTOR or PI3K  

作　　者：Stefan Kassumeh Sebastian Arrow AndréKafka Nikolaus Luft Siegfried G.Priglinger Armin Wolf Kirsten Eibl-Lindner Christian M.Wertheimer 

机构地区：[1]Department of Ophthalmology,University Hospital,LMU Munich,Munich 80336,Germany [2]Department of Ophthalmology,University Hospital,University Ulm,Ulm 89075,Germany

出　　处：《International Journal of Ophthalmology(English edition)》2022年第10期1569-1576,共8页国际眼科杂志（英文版）

摘　　要：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 24 h of treatment. Antiproliferative effects were evaluated separately after a 72-hour incubation of the cells with the pharmacological substance. Subsequently, the IC_(50) was calculated. Tumor cell death was investigated using a double stain apoptosis detection assay. 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/m TOR 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.

关 键 词：uveal melanoma SELUMETINIB trametinib erufosine ERLOTINIB 

分 类 号：R739.7[医药卫生—肿瘤]