Abstract
Purpose :
Insulin resistance was recently found to be associated with a worse prognosis in uveal melanoma (UM) patients, but the molecular mechanisms of this event are not known yet. The liver-derived hormone insulin-like growth factor-1 (IGF-1), which becomes more bioavailable under insulin resistance, is considered to be the major chemoattractant for the lethal UM metastases. In this study, we analyzed the role of IGF-1 in the expression of the high affinity glucose transporter GLUT3 and glucose uptake in UM cells. We also evaluated the efficacy of the flavonoid quercetin in suppressing the energy production and viability of UM cells.
Methods :
The UM cell lines 92.1 and OMM 2.5 were incubated at normoglycemic conditions (5.5 mM glucose) with or without IGF-1 (100 ng/ml) ± Quercetin for 1-3 days. GLUT3 and Ki-67 levels were determined by immunocytochemistry and -blotting. Glucose uptake and ATP levels were detected by the fluorescent glucose analog 6-NBDG and a luminescent microplate test, respectively. Viability was analyzed by the MTT, Live-Dead, and TUNEL assays. Nucleoli were visualized by silver staining.
Results :
IGF-1 led to an increase in the translocation of GLUT3 to the cell surface, uptake of the glucose analog 6-NBDG, ATP production, as well as the nucleolar size, viability, and proliferation of UM cells whereas quercetin could significantly suppress these events.
Conclusions :
IGF-1 may be conferring the UM cells an additional growth advantage by increasing the glucose uptake and energy production capacity. The flavonoid quercetin can be considered as a novel, natural, and immediately available therapy option to prevent the IGF-1 dependent survival of UM cells, which deserves further investigation.
This is a 2020 ARVO Annual Meeting abstract.