Effects of LIFR inhibition using EC359 on TNBC cells in obesity conditions

In a study using syngeneic BALB/c mice, the impact of a high-fat diet (HFD) on triple-negative breast cancer (TNBC) progression was investigated using 4T1 cells. Mice were fed either a low-fat diet (LFD) or HFD for six weeks before receiving orthotopic injections of 4T1 cells. Post-tumor formation, mice were randomized into three groups: LFD, HFD, and HFD with EC359 treatment. Results indicated that HFD significantly enhanced tumor growth, while EC359 treatment notably reduced HFD-induced TNBC progression. To explore underlying mechanisms, global RNA sequencing was performed on tumor tissues, revealing that HFD altered the expression of 578 genes compared to LFD, with 325 genes differentially expressed between the HFD and HFD + EC359 groups. Gene set enrichment analysis showed that HFD-related genes were linked to cytokine signaling, inflammation, stem cell pathways, TGFβ, metastasis, and epithelial–mesenchymal transition, all of which were downregulated with EC359 treatment. Nine tumors derived from mouse 4T1 syngeneic xenograft models were processed, 3 each for LFD, HFD and HFD+EC359 treatments were processed for transcriptomic profiling and comparisons between different conditions.