RT Journal Article SR Electronic T1 TU-100 Antagonizes the M2 Polarization Phenotype of Macrophages in the Tumor Microenvironment by Suppressing the TLR4/NF-GraphicB/STAT3 Axis JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 1985 OP 1992 DO 10.21873/anticanres.16359 VO 43 IS 5 A1 CHEN, SHUHAI A1 MORINE, YUJI A1 SAITO, YU A1 YAMADA, SHINICHIRO A1 TERAOKU, HIROKI A1 IKEMOTO, TETSUYA A1 SHIMADA, MITSUO YR 2023 UL http://ar.iiarjournals.org/content/43/5/1985.abstract AB Background/Aim: Macrophages are the most abundant immune cells in the tumor stroma, and their polarization states within the tumor microenvironment (TME) exert critical roles in tumorigenesis. TU-100 (Daikenchuto) is a commonly prescribed Japanese herbal medicine that has shown anti-cancer effects by regulating cancer-associated fibroblasts (CAFs) in the TME. However, its effects on tumor-associated macrophages (TAMs) remain unclear. Materials and Methods: TAMs were generated by macrophage exposure to tumor-conditioned medium (CM), and their polarization states were evaluated after TU-100 treatment. The underlying mechanism was further studied. Results: TU-100 exhibited little cytotoxicity over a range of doses in M0 macrophages and TAMs. However, it could antagonize the M2-like polarization of macrophages evoked by tumor-CM exposure. These effects might be caused by the inhibition of TLR4/NF-B/STAT3 signaling in the M2-like phenotype of macrophages. Interestingly, TU-100 antagonized the malignancy promoting effects of M2 macrophages on hepatocellular carcinoma cell lines in vitro. Mechanistically, the administration of TU-100 restrained the high expression of MMP-2, COX-2, and VEGF in TAMs. Conclusion: TU-100 may alleviate the progression of cancer by regulating the M2 polarization of macrophages within the TME, suggesting a viable therapeutic approach.