Pien Tze Huang exerts anti-tumor effect by promoting CSF-1R degradation and cleavage in tumor-associated macrophagesOA
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.
Jun-Jie Zhang;Han-Shi Guo;Jing-Na Yuan;Si-Yu Chen;Bei Li;Shi-Cong Wang;Chun-Dong Yu;Yi-Lin Hong
Xiamen Key Laboratory of Traditional Chinese Medicine Bio-engineering,School of Pharmacy,Xiamen Medical College,Fujian 361023,China State Key Laboratory of Cellular Stress Biology,Innovation Center for Cell Biology,School of Life Sciences,Xiamen University,Fujian 361104,ChinaState Key Laboratory of Cellular Stress Biology,Innovation Center for Cell Biology,School of Life Sciences,Xiamen University,Fujian 361104,ChinaState Key Laboratory of Cellular Stress Biology,Innovation Center for Cell Biology,School of Life Sciences,Xiamen University,Fujian 361104,ChinaCollege of Traditional Chinese Medicine,Fujian University of Traditional Chinese Medicine,Fujian 350122,ChinaOrdos Center for Disease Control and Prevention,Ordos,Inner Mongolia Autonomous Region 017010,ChinaFujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development,Fujian 363000,ChinaState Key Laboratory of Cellular Stress Biology,Innovation Center for Cell Biology,School of Life Sciences,Xiamen University,Fujian 361104,ChinaXiamen Key Laboratory of Traditional Chinese Medicine Bio-engineering,School of Pharmacy,Xiamen Medical College,Fujian 361023,China State Key Laboratory of Cellular Stress Biology,Innovation Center for Cell Biology,School of Life Sciences,Xiamen University,Fujian 361104,China
医药卫生
Pien Tze Huangcolorectal cancertumor-associated macrophagesCSF-1RTLR2-iRhom2-ADAM17immunotherapy
《Traditional Medicine Research》 2026 (11)
P.14-26,13
funding from the Natural Science Foundation of Fujian Province of China(No.2025J083282023J01249)the Natural Science Foundation of Xiamen Municipality(No.3502Z202571070)Zhangzhou Pien Tze Huang Pharmaceutical Co.Ltd(No.YHT-21036-N-2102).
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