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Pien Tze Huang exerts anti-tumor effect by promoting CSF-1R degradation and cleavage in tumor-associated macrophages 认领 引用
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作者 Jun-Jie Zhang Han-Shi Guo +5 位作者 Jing-Na Yuan Si-Yu Chen Bei Li Shi-Cong Wang Chun-Dong Yu Yi-Lin Hong 《Traditional Medicine Research》 2026年第11期14-26,共13页
Background:This study aimed to investigate the antitumor efficacy of Pien Tze Huang(PZH)in colorectal cancer(CRC)and elucidate its immunomodulatory mechanism,with a focus on tumor-associated macrophages(TAMs)and colon... Background:This study aimed to investigate the antitumor efficacy of Pien Tze Huang(PZH)in colorectal cancer(CRC)and elucidate its immunomodulatory mechanism,with a focus on tumor-associated macrophages(TAMs)and colony-stimulating factor 1 receptor(CSF-1R)signaling.Methods:Antitumor effects were evaluated in subcutaneous MC38 allograft and azoxymethane/dextran sulfate sodium(AOM/DSS)-induced CRC mouse models.TAMs infiltration was analyzed via immunohistochemistry and flow cytometry.Macrophage proliferation and migration were assessed by using MTT and Transwell assays.RNA sequencing,RT-qPCR,Western blotting,cycloheximide chase,inhibitor,polysome profiling,and gene silencing assays were performed to determine the mechanism underlying CSF-1R regulation.Results:PZH suppressed mouse CRC growth in both subcutaneous MC38 allograft and AOM/DSS-induced models,with its efficacy being partly dependent on reducing TAMs infiltration.In vitro assays further revealed that PZH impaired macrophage proliferation and migration.Mechanistically,PZH selectively downregulated CSF-1R via a multilayered program involving rapid posttranslational degradation through proteasomal and lysosomal pathways,as well as receptor proteolytic cleavage mediated by the TLR2-iRhom2-ADAM17 axis.Conclusion:Our experiments identify TAMs and CSF-1R as key cellular and molecular targets of PZH,thereby highlighting its ability to modulate TAMs within the tumor microenvironment(TME)and inhibit CRC progression.These results provide mechanistic insights into the immunomodulatory actions of PZH and identify CSF-1R as a promising target for macrophage-targeted therapies in CRC. 展开更多
关键词 Pien Tze Huang colorectal cancer tumor-associated macrophages CSF-1R TLR2-iRhom2-ADAM17 immunotherapy
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