Uveal Melanoma Cell Growth Is Inhibited by Aminoimidazole Carboxamide Ribonucleotide (AICAR) Partially Through Activation of AMP-Dependent Kinase

摘要: Purpose To evaluate the effects and mechanism of aminoimidazole carboxamide ribonucleotide (AICAR), an AMP-dependent kinase (AMPK) activator, on growth uveal melanoma cell lines. Methods Four different lines were treated with AICAR (1-4 mM). Cell was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. cycle analysis conducted flow cytometry; additionally, expression cell-cycle control proteins, transcription factors, downstream effectors AMPK determined RT-PCR Western blot. Results Aminoimidazole inhibited growth, induced S-phase arrest, led to activation. treatment associated inhibition eukaryotic translation initiation factor 4E-BP1 phosphorylation, a marker mammalian target rapamycin (mTOR) pathway activity. also downregulation cyclins A D, but had minimal phosphorylation ribosomal protein S6 or levels macroautophagy LC3B. The abolished dipyridamole, adenosine transporter inhibitor that blocks entry into cells. Treatment 5-iodotubericidin, which inhibits conversion its 5'-phosphorylated ribotide 5-aminoimidazole-4-carboxamide-1-D-ribofuranosyl-5'-monophosphate (ZMP; direct activator AMPK), reversed most growth-inhibitory effects, indicating some AICAR's antiproliferative are mediated at least partially through Conclusions proliferation activation A1 D1.