Abstract
<title>Abstract</title> <p>Background: Melanoma is a highly aggressive malignancy characterized by rapid progression, early metastasis, and resistance to therapy. Given its high metabolic demand, targeting systemic tumor metabolism may represent a novel therapeutic strategy. Methods: Artificial hibernation was induced in C57BL/6 mice bearing B16-F10 melanoma tumors using intraperitoneal administration of 5′-adenosine monophosphate (AMP). Tumor growth, metastatic burden, and metabolic activity were evaluated using histopathology and ¹⁸F-FDG PET imaging. Results: Artificial hibernation induced a reversible hypometabolic state and significantly inhibited tumor growth. By day 28 after cancer cells implantation, mean tumor volume was reduced from 1920.3 ± 289.1 mm³ in controls to 706.2 ± 76.88 mm³ in hibernated mice (~ 63.2%), while tumor weight decreased from 4.4 ± 0.69 g to 1.2 ± 0.3 g (~ 72.7%). Metastatic burden was also markedly suppressed, with lung metastatic nodules reduced from 15.5 ± 6.1 to 6.2 ± 1.5 (~ 60.0%) and lung weight decreased from 1.03 ± 0.20 g to 0.30 ± 0.01 g (~ 70.9%) 20 days after intravenous injection of cancer cells. FDG-PET imaging demonstrated global metabolic suppression, with tumor glucose uptake reduced from 2.65 ± 0.49 to 1.53 ± 0.34 (~ 42%) and skeletal muscle uptake reduced by ~ 63%. Importantly, FDG uptake within metastatic lung lesions was also significantly reduced (~ 50%), indicating pronounced metabolic suppression within metastatic colonies. Notably, metabolic suppression was maintained across different tumor sizes, indicating efficacy in both moderate and large tumors. Conclusion: Artificial hibernation significantly suppresses melanoma growth and metastasis through systemic metabolic modulation. These findings support hypometabolic therapy as a novel and potentially translatable strategy for the treatment of aggressive and advanced cancers.</p>