Study Of Scutellariae Radix Active Components On Macrophage-mediated Innate Anti-tumor Immunity

Although the main focus of immuno-oncology has been manipulated the adaptive immune system,tumor associated macrophages(TAMs)are the main infiltrating components of the tumor microenvironment(TME)and play a critical role in cancer progression.They are mainly divided into two different subtypes: macrophages with antitumor or killing activity are called M1 while tumor-promoting or healing macrophages are named M2.Therefore,controlling the polarization of TAMs is an important strategy for cancer treatment,but there is no particularly effective means to regulate the process.Here,combined systems pharmacology targets and pathways analysis strategy,we uncovered Scutellariae Radix(SR)has the potential to regulate TAMs polarization to inhibit the growth of non-small cell lung cancer(NSCLC).Firstly,systems pharmacology approach was used to reveal the active components of SR targeting macrophages in TME through compound target prediction and target-microenvironment phenotypic association analysis.Secondly,in vitro experiment verified that WBB(wogonin,baicalein and baicalin),the main active component of SR,initiated macrophages programming to M1-like macrophages,and promoted the apoptosis of tumor cells.Finally,we evidenced that WBB effectively inhibited tumor growth in LLC tumor-bearing mice and increased the infiltration of M1-type macrophages in TME.Overall,the systems pharmacology offers a strategy to understand the mechanism of polypharmacology of natural products targeting TME.