Abstract
Purpose: :
Uveal melanoma (UM) is the most common primary intra-ocular malignancy in adults. Despite the high accuracy of clinical diagnosis and advances in local treatment, more than 40% of UM patients will develop metastases that ultimately lead to death. It has been previously shown by our laboratory that the nuclear factor-kappa B (NF-ΚB), a transcription factor related to carcinogenesis, is highly expressed in UM specimens . Bortezomib is a NF-ΚB inhibitor, which received accelerated FDA approval to treat multiple myeloma patients refractory to previous therapies. Although the role of NF-ΚB in protecting skin melanoma cells from apoptosis and the effects of bortezomib in skin melanoma have received considerable interest recently, the role of NF-ΚB and bortezomib in UM has not yet been studied.
Methods: :
Four human UM cell lines and one human transformed uveal melanocyte cell line were assayed for proliferative ability under conditions of increasing concentrations of bortezomib.
Results: :
All UM cell lines exposed to bortezomib disclosed a very statistically significant decreased proliferation rate when compared to the control group.
Conclusions: :
The results of this study demonstrated that NF-ΚB is highly expressed in UM and that bortezomib treatment effectively decreases the proliferation rate of human UM cell lines. Recent advances in the development of drugs that down-regulate NF-ΚB signalling may therefore provide potential adjuvant modalities to conventional therapies in UM.
Keywords: melanoma • uvea • drug toxicity/drug effects