Dose-Dependent Angiogenic Effects of Intravenous Nicotinamide Riboside in Mice with a Lewis Lung Carcinoma Model

We studied the dose-dependent effects of the NAD+ precursor nicotinamide riboside (NR) on tumor angiogenesis in C57BL/6N mice with Lewis lung carcinoma. The pharmacological agent was repeatedly administered intravenously at doses of 300 and 450 mg/kg. Iimmunohistochemical analysis (CD34 class II, clone QBEnd 10) showed that the administration of NR at a dose of 450 mg/kg led to a significant increase in the density of tumor vessels in comparison with animals not treated with NR, while the area of tumor necrosis did not change significantly. These findings align with the RT-qPCR data, specifically the upregulation of Sirt2, the downregulation of Sirt1, Sirt3, and Parp1, and the absence of significant changes in the expression of Nos3 and Vegfa. These findings indicate a pro-angiogenic effect of a high dose of NR, which can be considered in the context of a "vascular normalization" strategy to enhance the delivery of chemotherapeutic agents.