Anti-tumor effect of flavonoids isolated from Bidens Pilosa L. by regulating the activity of myeloid-derived suppressor cells within the tumor microenvironment in mice

Ethnopharmacological relevance Colon cancer is one of the most common malignant tumors worldwide. Bidens pilosa L., an annual herb of the Asteraceae, has long been used to treat inflammatory-related illnesses, including cancer. As a population of immunosuppressive cells in the TME, MDSCs play a pivotal role in tumorigenesis and progression, and the effect of B. pilosa on MDSCs has rarely been reported. Aim of study To investigate the anti-tumor effect of a mixture of two flavonoids, MTF, isolated from B. pilosa, which showed immunotherapeutic activity in regulating the function of MDSCs in colon cancer. Materials and methods The regulatory effects of the flavonoid MTF on MDSCs differentiation and immune function were tested by qRT-PCR and flow cytometry. Its underlying immunotherapeutic mechanism, cytotoxicity, and anti-angiogenic activity were investigated using SIE luciferase/western blot, CCK-8/apoptosis, and MDSC-HUVEC co-culture assays, respectively. The in vivo anti-tumor activity of MTF was subsequently investigated in both CT26.WT and CT26.WT/MDSC syngeneic models. Results MTF and its components effectively depleted MDSCs by inhibiting their differentiation and inducing apoptosis, thereby restoring suppressed CD4 + T cell function. In vivo, MTF not only reduced intratumoral MDSCs but also counteracted MDSC-driven angiogenesis, leading to inhibited tumor growth and enhanced sensitivity to 5-FU treatment. Conclusion Flavonoid MTF showed a good antitumor effect in mice by regulating MDSCs activity in the TME, which contributes to the clinical use of this traditional herb.