Gambogenic acid induces cell growth inhibition, cell cycle arrest and metastasis inhibition in choroidal melanoma in a dose-dependent manner

The aim of the present study was to explore the effects of gambogenic acid (GNA) on the malignant behaviors of choroidal melanoma cells, including cell viability, cell cycle, migration and invasion, and to elucidate the underlying regulatory mechanism. The human choroidal melanoma cell line OCM-1 was treated with different concentrations of GNA and cell viability, colony formation ability, cell cycle, migration and invasion were analyzed. Additionally, cells were incubated with or without LY294002, a specific inhibitor of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, for 24 h. Levels of cell cycle-associated proteins (cyclin D1, cyclin E, cyclindependent kinase 2 and P21), epithelial-mesenchymal transition (EMT)-associated molecules (epithelial-cadherin, alpha-smooth muscle actin and vimentin) and phosphorylated (p)-AKT/AKT were determined using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The results demonstrated that GNA significantly inhibited cell viability and induced cell cycle arrest at the G0/G1 phase in a dose-dependent manner (P< 0.01). Furthermore, GNA administration significantly suppressed cell migration and invasion in a dose-dependent manner (P< 0.01). Treatment with GNA or LY294002 induced a marked decrease in the expression of p-AKT/AKT, a significant downregulation in cell cycleassociated molecules (P< 0.01), and a significant decrease in cell viability (P< 0.01). Co-treatment with LY294002 and GNA had an additive effect on the growth of OCM-1 cells. In conclusion, the results of the present study suggest that treatment with GNA may inhibit cell viability and induce G0/G1 arrest. Furthermore, GNA may also inhibit cell metastasis via regulating EMT-associated molecules. The PI3K/Akt signaling pathway may be a key mechanism involved in the progression of choroidal melanoma, and GNA may serve as a potential therapeutic reagent for the treatment of this disease.