Saikosaponin A (SSA) has been revealed to have anti-breast cancer (BC) effect. However, the association between SSA and BC glycolysis is obscure. We want to probe the function and mechanism of SSA on BC glycolysis. Kaplan-Meier plotter revealed the relationship between STAT3 and the survival curve of BC. The protein kinase B (Akt)/signal transducer and activator of transcription 3 (STAT3) pathway and the viability in cells treated with or without 0, 5, 10, and 15 μM SSA were assessed by Western blot and cell counting kit-8. The biological behaviors, lactate, and ATP contents, glucose uptake, and Akt/STAT3 pathway-related markers in BC cells treated with colivelin or SSA were evaluated using cell function experiments, kit, and Western blot. Then, the impacts of colivelin and SSA on BC cells were tested again. The overexpressions of p-STAT3 and p-Akt in BC cells were weakened by 5, 10, and 15 μM SSA. Colivelin boosted the BC cell viability and proliferation and impeded apoptosis, while SSA did the opposite. Meanwhile, colivelin intensified lactate and ATP contents, glucose uptake, and Akt/STAT3 pathway-related markers level in BC cells, while SSA was the opposite. The modulation of SSA on the biological behavior, lactate and ATP productions, glucose uptake, and Akt/STAT3 pathway was rescued by colivelin. Our research unveiled new insights into SSA as a valuable candidate therapeutic agent for weakening glycolysis, and protruded the Akt/STAT3 pathway as a latent molecular target for SSA and glycolysis modulation.© 2023 John Wiley & Sons Ltd.
