Bravo-Filho Vasco, Logan Patrick, Zoroquiain Pablo, Aldrees Sultan, Vilà Natàlia, Oweida Ayman, Belfort Neto Rubens, Burnier Miguel N
The Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, Quebec, Canada.
Ophthalmology and Visual Sciences Department, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Arq Bras Oftalmol. 2019 Jan-Feb;82(1):38-44. doi: 10.5935/0004-2749.20190004. Epub 2018 Nov 1.
To evaluate the effects of ranibizumab and amfenac in human uveal melanoma cell lines and to explore the ability of these compounds to sensitize uveal melanoma cells to radiation therapy.
The 92.1 human uveal melanoma cell line was cultured and subjected to the proposed treatment (ranibizumab, amfenac, and a combination of both). Proliferation, migration, and invasion assays of the 92.1 uveal melanoma cell line were assessed after pretreatment with ranibizumab (125 mg/mL), amfenac (150 nM), or a combination of both. In addition, proliferation rates were assessed after treatment with ranibizumab and amfenac, and the cells were subsequently exposed to various radiation doses (0, 4, and 8 Gy).
Proliferation assay: cells treated with a combination of ranibizumab and amfenac had lower proliferation rates than controls (p=0.016) and than those treated with only ranibizumab (p=0.033). Migration assay: a significantly lower migration rate was observed in cells treated with amfenac than the control (p=0.014) and than those treated with ranibizumab (p=0.044). Invasion assay: there were no significant differences among the studied groups. Irradiation exposure: in the 4 Gy dose group, there were no significant differences among any groups. In the 8 Gy dose group, treatment with ranibizumab, amfenac, and their combination prior to application of the 8 Gy radiation led to a marked reduction in proliferation rates (p=0.009, p=0.01, and p=0.034, respectively) compared with controls.
Combination of ranibizumab and amfenac reduced the proliferation rate of uveal melanoma cells; however, only amfenac monotherapy significantly decreased cell migration. The radiosensitivity of the 92.1 uveal melanoma cell line increased following the administration of ranibizumab, amfenac, and their combination. Further investigation is warranted to determine if this is a viable pretreatment strategy to render large tumors amenable to radiotherapy.
评估雷珠单抗和安芬那酸对人葡萄膜黑色素瘤细胞系的影响，并探讨这些化合物使葡萄膜黑色素瘤细胞对放射治疗敏感的能力。
培养92.1人葡萄膜黑色素瘤细胞系，并进行拟议的治疗（雷珠单抗、安芬那酸以及两者联合）。在用雷珠单抗（125mg/mL）、安芬那酸（150nM）或两者联合进行预处理后，评估92.1葡萄膜黑色素瘤细胞系的增殖、迁移和侵袭试验。此外，在用雷珠单抗和安芬那酸治疗后评估增殖率，随后将细胞暴露于不同的辐射剂量（0、4和8Gy）。
增殖试验：用雷珠单抗和安芬那酸联合治疗的细胞增殖率低于对照组（p=0.016），也低于仅用雷珠单抗治疗的细胞（p=0.033）。迁移试验：在用安芬那酸治疗的细胞中观察到迁移率明显低于对照组（p=0.014），也低于用雷珠单抗治疗的细胞（p=0.044）。侵袭试验：各研究组之间无显著差异。辐射暴露：在4Gy剂量组中，各组之间无显著差异。在8Gy剂量组中，在施加8Gy辐射之前用雷珠单抗、安芬那酸及其联合治疗导致增殖率显著降低（分别为p=0.009、p=0.01和p=0.034），与对照组相比。
雷珠单抗和安芬那酸联合降低了葡萄膜黑色素瘤细胞的增殖率；然而，只有安芬那酸单药治疗显著降低了细胞迁移。在给予雷珠单抗、安芬那酸及其联合治疗后，92.1葡萄膜黑色素瘤细胞系的放射敏感性增加。有必要进一步研究以确定这是否是使大肿瘤适合放疗的可行预处理策略。
