Imeglimin Exerts Anti-Tumor Activity in Multiple Myeloma Through Affecting Energy Metabolism and Downregulating IL-16 Expression

Background: Imeglimin (IME) is a novel oral anti-diabetic agent with a similar chemical structure to metformin, which has shown broad-spectrum anti-tumor activity. However, the activity of imeglimin on tumor cells remains unclear. This study investigated the effects of IME on multiple myeloma (MM) cells and explored the underlying mechanisms.

Methods: The effects of IME on MM cell proliferation were evaluated in vitro using MM cell lines and in MM cell-derived xenograft (CDX) models. Seahorse metabolic analyses and RNA-Seq were performed in IME-treated and control MM cell lines. Single-cell transcriptomic data were further analyzed to assess the role of IL-16 in the bone marrow microenvironment.

Results: IME inhibited MM cell proliferation and tumor growth in MM cell-derived xenograft (CDX) models by inducing G1/G0 cell cycle arrest. IME suppressed Oxidative Phosphorylation and promoted glycolysis. IL-16 mRNA expression was downregulated, and multiple cytokine-cytokine receptor interaction pathways were altered following IME treatment. The anti-MM effect of IME was partly mediated by increased lactate production and decreased IL-16 expression. Single-cell transcriptomic data further demonstrated that IL-16 plays an important role in the bone marrow microenvironment of MM.

Conclusions: These findings suggest that IME may represent a novel approach for targeting IL-16 and energy metabolism in the treatment of MM.

IL‐16; energy metabolism; imeglimin; multiple myeloma.