Fluorescence lifetime imaging microscopy for metabolic analysis of LDHB inhibition in triple negative breast cancer

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with no targeted treatments currently available. TNBC cells participate in metabolic symbiosis, a process that optimizes tumor growth by balancing metabolic processes between glycolysis and oxidative phosphorylation through increased activity by the enzyme lactate dehydrogenase B (LDHB). Metabolic symbiosis allows oxidative cancer cells to function at a similar rate as glycolytic cancer cells, increasing overall metabolic activity and proliferation. Here, fluorescence lifetime imaging microscopy (FLIM) is used to analyze the metabolism of TNBC cells with inhibition of LDHB using a multiphoton microscope to measure the fluorescent lifetimes of two metabolic coenzymes, NAD(P)H and FAD. LDHB is inhibited via an indole derivative known as AXKO-0046 in varying concentrations. Understanding how TNBC cell metabolism changes due to LDHB inhibition will provide further insight into metabolic symbiosis and potential new TNBC treatment options.