Whitman believes that people in cities should establish a harmonious relationship between humans and nature.In his urban imagination,humans are a common link in the entire ecosystem.As a part of heaven and earth,every...Whitman believes that people in cities should establish a harmonious relationship between humans and nature.In his urban imagination,humans are a common link in the entire ecosystem.As a part of heaven and earth,everything is one.Through dialogue with nature,Whitman explored that man and nature should be equal and harmonious.Whitman embodies the unique urban ecological poetics in his essay the Riverbank of the Ferry Crossing Last Winter,which contains Chinese classical thought of harmony between man and nature.展开更多
HuR(human antigen R), an mRNA-binding protein responsible for poor prognosis in nearly all kinds of malignancies, is a potential anti-tumor target for drug development. While screening HuR inhibitors with a fluorescen...HuR(human antigen R), an mRNA-binding protein responsible for poor prognosis in nearly all kinds of malignancies, is a potential anti-tumor target for drug development. While screening HuR inhibitors with a fluorescence polarization(FP) based high-throughput screening(HTS) system, the clinically used drug eltrombopag was identified. Activity of eltrombopag on molecular level was verified with FP, electrophoretic mobility shift assay(EMSA), simulation docking and surface plasmon resonance(SPR). Further, we showed that eltrombopag inhibited in vitro cell proliferation of multiple cancer cell lines and macrophages, and the in vivo anti-tumor activity was also demonstrated in a 4T1 tumor-bearing mouse model. The in vivo data showed that eltrombopag was efficient in reducing microvessels in tumor tissues. We then confirmed the HuR-dependent anti-angiogenesis effect of eltrombopag in 4T1 cells and RAW264.7 macrophages with qRT-PCR, HuR-overexpression and HuR-silencing assays, RNA stability assays, RNA immunoprecipitation and luciferase assays. Finally, we analyzed the in vitro anti-angiogenesis effect of eltrombopag on human umbilical vein endothelial cells(HUVECs) mediated by macrophages with cell scratch assay and in vitro Matrigel angiogenesis assay. With these data, we revealed the HuR-dependent anti-angiogenesis effect of eltrombopag in breast tumor, suggesting that the existing drug eltrombopag may be used as an anti-cancer drug.展开更多
文摘Whitman believes that people in cities should establish a harmonious relationship between humans and nature.In his urban imagination,humans are a common link in the entire ecosystem.As a part of heaven and earth,everything is one.Through dialogue with nature,Whitman explored that man and nature should be equal and harmonious.Whitman embodies the unique urban ecological poetics in his essay the Riverbank of the Ferry Crossing Last Winter,which contains Chinese classical thought of harmony between man and nature.
基金supported by National Natural Science Foundation of China(81573579)the New Interdisciplinary Subject Funding Program for Shanghai Traditional Chinese Medicine(E2-F18003,China)+3 种基金Shanghai Municipal Education Commission(SMEC,2019-01-07-00-10-E00072,China)Science and Technology Commission of Shanghai Municipality(STCSM,18401933500,China)Postdoctoral Science Foundation of China(A2-X1802408)Shanghai Municipal Commission of Health and Family Planning(2018YQ003,China)
文摘HuR(human antigen R), an mRNA-binding protein responsible for poor prognosis in nearly all kinds of malignancies, is a potential anti-tumor target for drug development. While screening HuR inhibitors with a fluorescence polarization(FP) based high-throughput screening(HTS) system, the clinically used drug eltrombopag was identified. Activity of eltrombopag on molecular level was verified with FP, electrophoretic mobility shift assay(EMSA), simulation docking and surface plasmon resonance(SPR). Further, we showed that eltrombopag inhibited in vitro cell proliferation of multiple cancer cell lines and macrophages, and the in vivo anti-tumor activity was also demonstrated in a 4T1 tumor-bearing mouse model. The in vivo data showed that eltrombopag was efficient in reducing microvessels in tumor tissues. We then confirmed the HuR-dependent anti-angiogenesis effect of eltrombopag in 4T1 cells and RAW264.7 macrophages with qRT-PCR, HuR-overexpression and HuR-silencing assays, RNA stability assays, RNA immunoprecipitation and luciferase assays. Finally, we analyzed the in vitro anti-angiogenesis effect of eltrombopag on human umbilical vein endothelial cells(HUVECs) mediated by macrophages with cell scratch assay and in vitro Matrigel angiogenesis assay. With these data, we revealed the HuR-dependent anti-angiogenesis effect of eltrombopag in breast tumor, suggesting that the existing drug eltrombopag may be used as an anti-cancer drug.