Background:Gastric cancer(GC)is a prevalent cause of death.3,9-Di-O-methylnissolin(DOM)is a flavonoid isolated from Astragalus membranaceus.It has anticancer and anti-inflammatory effects,but its effect and mechanismo...Background:Gastric cancer(GC)is a prevalent cause of death.3,9-Di-O-methylnissolin(DOM)is a flavonoid isolated from Astragalus membranaceus.It has anticancer and anti-inflammatory effects,but its effect and mechanismof actiononGCarenot very clear.Methods:The appropriate concentration was selected after observing the effects of varying concentrations of DOM on the viability of GC cells,which was examined through the cell counting kit-8(CCK-8)assay.The receptor-interacting protein kinase 2(RIPK2)overexpression plasmid was transfected into GC cells,which were then treated with DOM.Cell cycle and proliferation,RIPK2 levels,and inflammatory factor levels were evaluated by flow cytometry,cell colony formation assay,Hoechst 33,258 fluorescence,5-ethynyl-2′-deoxyuridine(EdU)assay,Transwell assay,immunofluorescence,and enzyme-linked immunosorbent assay(ELISA),respectively.The nuclear factor kappa-B(NF-κB)pathway was detected using immunofluorescence andWestern blot.Results:The appropriate concentrations of DOM were found to be 200,400,and 800μg/mL.At these concentrations,in GC cells,DOMcould significantly reduce EdU-positive cells;decrease the colony formation,migration,and invasion rates;block the cell cycle;increase theHoechst 33,258 fluorescence intensity and apoptosis rate;andsignificantly reduce p-IκBαand p-NF-κB p65 expressions.Moreover,DOMnotably reduced the high level of RIPK2.After the overexpression of RIPK2,these effects were significantly reversed in GC cells,and interleukin(IL)-1βand IL-6 contents were clearly elevated.Conclusion:DOMcan suppress the level of RIPK2 and inhibit the activation of the NF-κB signaling,thereby reducing inflammation;inhibiting the malignant progression of GC cells;and promoting cycle arrest.展开更多
1 MHC-I Loss in the Immune Evasion of Cancer Cells Pancreatic ductal adenocarcinoma(PDAC)is a lethal cancer with a poor prognosis due to its aggressive nature and late detection.Recently,new discoveries in PDAC demons...1 MHC-I Loss in the Immune Evasion of Cancer Cells Pancreatic ductal adenocarcinoma(PDAC)is a lethal cancer with a poor prognosis due to its aggressive nature and late detection.Recently,new discoveries in PDAC demonstrated receptor-interacting protein kinase 2(RIPK2)triggering immune evasion.Mechanistically,RIPK2 drives the desmoplastic tumor microenvironment(TME)and restricts the activation and density of tumor-infiltrating effector T cells by impairing the expression of major histocompatibility complex class I(MHC-I)[1].This process might be relevant in different solid cancer entities as illustrated by analyzing publicly available databases.展开更多
基金funded by the Hospital Fund of The First Hospital of Lanzhou University(grant number ldyyyyn2023-46)the Science and Technology Project of Gansu Province Key Research and Development Program(grant number 21YF5FA120)+1 种基金the Gansu Province Health Industry Research Project(grant number GSWSKY2020-12)the National Natural Science Foundation of China(grant number 82160498).
文摘Background:Gastric cancer(GC)is a prevalent cause of death.3,9-Di-O-methylnissolin(DOM)is a flavonoid isolated from Astragalus membranaceus.It has anticancer and anti-inflammatory effects,but its effect and mechanismof actiononGCarenot very clear.Methods:The appropriate concentration was selected after observing the effects of varying concentrations of DOM on the viability of GC cells,which was examined through the cell counting kit-8(CCK-8)assay.The receptor-interacting protein kinase 2(RIPK2)overexpression plasmid was transfected into GC cells,which were then treated with DOM.Cell cycle and proliferation,RIPK2 levels,and inflammatory factor levels were evaluated by flow cytometry,cell colony formation assay,Hoechst 33,258 fluorescence,5-ethynyl-2′-deoxyuridine(EdU)assay,Transwell assay,immunofluorescence,and enzyme-linked immunosorbent assay(ELISA),respectively.The nuclear factor kappa-B(NF-κB)pathway was detected using immunofluorescence andWestern blot.Results:The appropriate concentrations of DOM were found to be 200,400,and 800μg/mL.At these concentrations,in GC cells,DOMcould significantly reduce EdU-positive cells;decrease the colony formation,migration,and invasion rates;block the cell cycle;increase theHoechst 33,258 fluorescence intensity and apoptosis rate;andsignificantly reduce p-IκBαand p-NF-κB p65 expressions.Moreover,DOMnotably reduced the high level of RIPK2.After the overexpression of RIPK2,these effects were significantly reversed in GC cells,and interleukin(IL)-1βand IL-6 contents were clearly elevated.Conclusion:DOMcan suppress the level of RIPK2 and inhibit the activation of the NF-κB signaling,thereby reducing inflammation;inhibiting the malignant progression of GC cells;and promoting cycle arrest.
文摘1 MHC-I Loss in the Immune Evasion of Cancer Cells Pancreatic ductal adenocarcinoma(PDAC)is a lethal cancer with a poor prognosis due to its aggressive nature and late detection.Recently,new discoveries in PDAC demonstrated receptor-interacting protein kinase 2(RIPK2)triggering immune evasion.Mechanistically,RIPK2 drives the desmoplastic tumor microenvironment(TME)and restricts the activation and density of tumor-infiltrating effector T cells by impairing the expression of major histocompatibility complex class I(MHC-I)[1].This process might be relevant in different solid cancer entities as illustrated by analyzing publicly available databases.
