Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Department of Medicine, Clinic III, Hematology, Oncology and Palliative Medicine, University Medical Center Rostock, Rostock, Germany.
Anticancer Res. 2024 Sep;44(9):3843-3848. doi: 10.21873/anticanres.17210.
BACKGROUND/AIM: Uveal melanoma (UM) represents a prevailing primary intraocular malignancy, with a limited median overall survival among metastatic patients, and most tumors lack RAF/RAS mutations. The pan-RAF inhibitor LY3009120 has demonstrated valuable anti-tumor effects in a wide range of RAF/RASmut and wild-type (WT) tumor models. This study aimed to evaluate the antitumor effect of LY3009120 on 92-1 UM cell line.
The effect of the pan-RAF inhibitor LY3009120 on cell proliferation, metabolic activity, biomass, early and late apoptosis/necrosis, and morphology was characterized in vitro (0.1-5 μM for 48 h/72 h). Furthermore, targeted panel sequencing was used to characterize the mutational landscape of the human 92-1 UM cell line.
LY3009120 showed a significant concentration-dependent anti-proliferative effect on 92-1 cells. Cell proliferation and viability were significantly reduced at the lowest effective concentration of 0.5 μM (at 48 and 72 h, p<0.001). Furthermore, LY3009120 caused significant early apoptosis and late apoptosis/necrosis in 92-1 cells at 5 μM. Except for TP53, NGS showed that all 49 additional analysed genes (Oncomine myeloid panel) of 92-1 were wild-type, including BRAF, NRAS, and KRAS.
The pan-RAF inhibitor LY3009120 demonstrated a significant anti-tumor effect on human UM cell line 92-1 independent of the molecular BRAF and RAS mutational status.
背景/目的：葡萄膜黑色素瘤（UM）是一种主要的眼内原发性恶性肿瘤，转移性患者的总体中位生存期有限，且大多数肿瘤缺乏 RAF/RAS 突变。泛 RAF 抑制剂 LY3009120 在广泛的 RAF/RASmut 和野生型（WT）肿瘤模型中显示出有价值的抗肿瘤作用。本研究旨在评估 LY3009120 对 92-1UM 细胞系的抗肿瘤作用。
体外（48 小时/72 小时，0.1-5 μM）研究了泛 RAF 抑制剂 LY3009120 对细胞增殖、代谢活性、生物量、早期和晚期凋亡/坏死以及形态的影响。此外，还使用靶向面板测序来描述人 92-1UM 细胞系的突变景观。
LY3009120 对 92-1 细胞表现出显著的浓度依赖性抗增殖作用。在最低有效浓度 0.5 μM（48 小时和 72 小时，p<0.001）时，细胞增殖和活力明显降低。此外，LY3009120 在 5 μM 时引起 92-1 细胞明显的早期凋亡和晚期凋亡/坏死。除 TP53 外，NGS 显示 92-1 的 49 个额外分析基因（Oncomine 髓样面板）均为野生型，包括 BRAF、NRAS 和 KRAS。
泛 RAF 抑制剂 LY3009120 对人 UM 细胞系 92-1 表现出显著的抗肿瘤作用，而与分子 BRAF 和 RAS 突变状态无关。
