A promising magnesium-related alloy with metabolic reprogramming and antitumor effects in hepatocellular and pancreatic cancer.

Abstract

Hepatocellular and pancreatic cancers are highly aggressive malignancies with dismal clinical outcomes, highlighting an urgent need for new therapeutic strategies. Magnesium-related alloys, widely explored for their biocompatibility and bioactivity, are attractive candidates for biliary and pancreatic duct stents. However, their antitumor potential and underlying mechanisms remain incompletely defined. Here, we systematically characterized the physicochemical properties and anticancer activities of a panel of magnesium-related alloy powders and identified an aluminum-magnesium (Al-Mg) alloy as the most potent candidate. Compared with pure Mg, Al-Mg rods exhibited stronger antitumor efficacy together with more controllable degradation. <i>In vitro</i> and <i>in vivo</i> assays confirmed that Al-Mg significantly inhibited hepatocellular carcinoma and pancreatic cancer progression. Integrated metabolomic and transcriptomic analyses indicated that Al-Mg activates AMPK signaling and suppresses purine and pyrimidine metabolism, consistent with metabolic reprogramming that limits tumor cell proliferation. Furthermore, single-cell and spatial transcriptomic analyses delineated Al-Mg-sensitive tumor cell subpopulations and mapped their spatial distribution within pancreatic cancer tissues. Collectively, these findings position Al-Mg as a promising antitumor material and provide a mechanistic framework supporting the development of magnesium-related alloys for local oncologic intervention.