Purchase this article with an account.
Debra-Meghan Sanft, Sultan Aldrees, Sabrina Bergeron, Jade Lasiste, Denise Miyamoto, Miguel N Burnier; The effect of SIRT1 inhibition by EX527 on uveal melanoma cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3956.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
SIRT1 expression has previously been documented in a variety of malignancies, including uveal melanoma (UM), and is believed to inactivate proteins involved in tumor suppression and DNA repair. EX527 is a specific SIRT1 inhibitor that has been shown to decrease cutaneous melanoma proliferation in culture. Herein, we investigated the effects of EX527 on the proliferation and migration of a human uveal melanoma cell line.
The OCM-1 cell line was used to test the effect of EX527 on its proliferative and migratory abilities. For the proliferation assay, the cells were seeded in triplicates at a concentration of 5000 cells/well in a 96-well plate. The cells were serum starved for 24 hours and then the drug was added in three different concentrations: 10, 25, and 50 µM for 48 hours. At the end of the experiment, the number of cells in each well were estimated using a colorimetric cellular proliferation. To test the effects of EX527 on migration, the experiment with the same drug concentrations was repeated using a cell migration assay as per manufacturer instructions.
Inhibiting SIRT1 using EX527 decreased the proliferation rate of the tested cell line in a dose dependent manner. Compared to the control, 10 µM of EX527 did not significantly decrease proliferation (P=0.07). However, higher doses (25 and 50 µM) significantly inhibited proliferation (P<0.01). Similarly, EX527 decreased the number of migrating cells in a dose dependent manner. Compared to 10 µM, 25 µM of EX527 did not significantly decrease migration (P=0.22). However, the highest concentration (50 µM) significantly decreased migration compared to 10 and 25 µM (P<0.01). The control group had the highest migration.
To the best of our knowledge, this is the first study to evaluate the effects of a specific SIRT1 inhibitor; EX527, on UM cells in vitro. At physiologically relevant doses, EX527 inhibited both UM cell migration and proliferation, making it a suitable candidate for future studies. The effects of this drug should be explored in an animal model of this disease to determine administration routes, doses, and potential side effects.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only