Abstract
Purpose:
Uveal Melanoma (UM) is the most common primary intraocular tumor in adults and even with recent progress in treating the primary tumor, mortality rate is still high. Also, some tumors are too large at presentation and do not qualify for radiation therapy, which is the standard treatment. Therefore, there is a need for alternative treatment options. Our purpose was to evaluate the effects of ranibizumab in association with amfenac in human uveal melanoma cell lines. Moreover, we tested the ability of these compounds to sensitize uveal melanoma cells to radiation therapy.
Methods:
Proliferation and migration of the 92.1 uveal melanoma cell line were assessed after pretreatment with ranibizumab (125 microg/ml) or amfenac (150 nM), and the combination of both compounds. In addition, proliferation rates were assessed after treatment with ranibizumab and amfenac and subsequent radiation exposure. After treatment with ranibizumab and amfenac, cells were exposed to various doses of radiation: 0, 4, and 8 Gy. An MTT assay was used to assess proliferation rates 48 hours after radiation exposure, and these values were compared to control cells (without radiation and without treatment, but with radiation).
Results:
Cells treated with ranibizumab and amfenac had lower proliferation rates compared to controls (P=0.016), and to the group treated only with ranibizumab (P=0.033). Migration was only statistically lower in the group treated with amfenac relative to the control (P=0.014). Treatment with ranibizumab, amfenac, and the combination of both prior to the 8 Gy radiation dose led to a marked reduction in proliferation rates (P=0.009; P=0.01; P=0.034; respectively). There was no statistical difference between the three treatment groups with the 8 Gy dose.
Conclusions:
The combination of ranibizumab and amfenac decreased the proliferation rate of uveal melanoma cells; however, only amfenac monotherapy significantly decreased cell migration. Other studies as an animal model, would help us to clarify if using this association we could avoid tumor growth. The radiosensitivity of the 92.1 UM cell line was increased by the administration of ranibizumab, amfenac, and combination therapy. Further investigation is warranted to determine if this treatment is a viable pretreatment strategy to render large tumors amenable to radiotherapy.