PT  - JOURNAL ARTICLE
AU  - CHEN, SHUHAI
AU  - MORINE, YUJI
AU  - SAITO, YU
AU  - YAMADA, SHINICHIRO
AU  - TERAOKU, HIROKI
AU  - IKEMOTO, TETSUYA
AU  - SHIMADA, MITSUO
TI  - TU-100 Antagonizes the M2 Polarization Phenotype of Macrophages in the Tumor Microenvironment by Suppressing the TLR4/NF-<img src="pending:yes" l:ref-type="journal" hwp:journal="anticanres" hwp:volume="43" hwp:issue="5" hwp:article="1985" l:sub-ref="inline-graphic-1" l:type="image/*" class="inline-graphic" alt="Graphic"/>B/STAT3 Axis
AID  - 10.21873/anticanres.16359
DP  - 2023 May 01
TA  - Anticancer Research
PG  - 1985--1992
VI  - 43
IP  - 5
4099  - http://ar.iiarjournals.org/content/43/5/1985.short
4100  - http://ar.iiarjournals.org/content/43/5/1985.full
SO  - Anticancer Res2023 May 01; 43
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.