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.