Background:Shuangshen granule s(SSGs) are extensively utilized for the treatment of lung cancer in China and have been reported to possess tumor-protective and anti-metastatic effects.Therefore,it is crucial to unders...Background:Shuangshen granule s(SSGs) are extensively utilized for the treatment of lung cancer in China and have been reported to possess tumor-protective and anti-metastatic effects.Therefore,it is crucial to understand the precise mechanism.Building upon the findings of our previous study,the objective of the present study was to explore the impact of S SGs on the sphingosine-1-phosphate receptor-1(S1PR1)/signal transducer and activator of transcription 3(STAT3) axis,as well as the recruitment of myeloid-derived suppressor cells(MDSCs) during the formation of the premetastatic niches(PMNs).Methods:In a mouse xenograft model utilizing Lewis lung carcinoma(LLC) cells that express green fluorescent protein(GFP),the initiation of lung metastasis was monitored every three days until day 35 following transplantation.Lung metastasis,MD SC recruitment,the expression of PMN and S1PR1/STAT3 axis biomarkers,as well as the blood levels of granulocyte-mac rophage colony-stimulating factor(GM-CSF) and transforming growth factor-β(TGF-β) were assessed in the SSG treatment and control groups.Results:The LLC cells did not reach the lung until 14-17 days following subcutaneous implantation,which was concurrent with the formation of lung PMNs.S SG significantly postponed the initiation of lung metastasis and reduced the recruitment of MDSCs to the lung PMNs.S SG also suppre ssed the S1PR1/STAT3 axis in tumor tissue s,bone marrow,and lung PMNs.Additionally,SSG suppres sed the blood levels of GM-CSF and TGF-β,as well as the PMN markers,matrix metalloproteinase-9 and versican.Conclusion:Our findings suggested that SSG suppressed the development of MD SC-mediated PMNs by inhibiting the S1PR1/STAT3 axis,consequently postponing the initiation of lung metastasis.展开更多
基金supported by the Special Training of Scientific and Technological Talents,China Academy of Chinese Medical Sciences (grant number ZZ13-YQ-023,ZZ13-YQ-028)the National Natural Science Foundation of China(grant number 82174465,82074338,82274609,82104961,82174463)+7 种基金the Beijing Municipal Science and Technology Commission (grant number Z181100001618006)Scientificand Technological Innovation Project of China Academy of Chinese Medical Sciences (grant number CI2021A01810,CI2021A01814,CI2021A01808,CI2021B009)Traditional Chinese Medicine Innovation Team Project of the National Administration of Traditional Chinese Medicine(grant number ZYYCXTD-C-202205)Central High-Level Traditional Chinese Medicine Hospital Clinical Research and Achievement Transformation Capacity Enhancement Project-Special Project Inheriting the Academic Experienceof Renowned Traditional Chinese Medicine Experts(HLCMHPP2023012)China Academy of Chinese Medical Sciences Special Project for Research and Development of Superior Diseases,Hospital Preparations,New Drugs(ZZ15-XY-PT-01)Xu Hang Project for Cultivating Young Top Talents at Guang'anmen Hospital (CZ40908)The Fundamental Research Funds for the Central Public Welfare Research Institutes (ZZ17XRZ-023)Clinical Research Expenses of the Central High-level Hospital of Traditional Chinese Medicine (HLCMHPP2023101)
文摘Background:Shuangshen granule s(SSGs) are extensively utilized for the treatment of lung cancer in China and have been reported to possess tumor-protective and anti-metastatic effects.Therefore,it is crucial to understand the precise mechanism.Building upon the findings of our previous study,the objective of the present study was to explore the impact of S SGs on the sphingosine-1-phosphate receptor-1(S1PR1)/signal transducer and activator of transcription 3(STAT3) axis,as well as the recruitment of myeloid-derived suppressor cells(MDSCs) during the formation of the premetastatic niches(PMNs).Methods:In a mouse xenograft model utilizing Lewis lung carcinoma(LLC) cells that express green fluorescent protein(GFP),the initiation of lung metastasis was monitored every three days until day 35 following transplantation.Lung metastasis,MD SC recruitment,the expression of PMN and S1PR1/STAT3 axis biomarkers,as well as the blood levels of granulocyte-mac rophage colony-stimulating factor(GM-CSF) and transforming growth factor-β(TGF-β) were assessed in the SSG treatment and control groups.Results:The LLC cells did not reach the lung until 14-17 days following subcutaneous implantation,which was concurrent with the formation of lung PMNs.S SG significantly postponed the initiation of lung metastasis and reduced the recruitment of MDSCs to the lung PMNs.S SG also suppre ssed the S1PR1/STAT3 axis in tumor tissue s,bone marrow,and lung PMNs.Additionally,SSG suppres sed the blood levels of GM-CSF and TGF-β,as well as the PMN markers,matrix metalloproteinase-9 and versican.Conclusion:Our findings suggested that SSG suppressed the development of MD SC-mediated PMNs by inhibiting the S1PR1/STAT3 axis,consequently postponing the initiation of lung metastasis.
