AIM:To investigate YM155’s effect on retinal pigment epithelium(RPE)cells’viability and the potential regulatory mechanisms.METHODS:Human immortalized RPE cell lines(ARPE-19 cell line)were processed with YM155 and e...AIM:To investigate YM155’s effect on retinal pigment epithelium(RPE)cells’viability and the potential regulatory mechanisms.METHODS:Human immortalized RPE cell lines(ARPE-19 cell line)were processed with YM155 and epidermal growth factor(EGF).ARPE-19 cell viability was detected by methyl thiazolyl tetrazolium assay,and apoptosis was tested by flow cytometry assay.ARPE-19 cell proliferation was assessed with bromodeoxyuridine tagged incorporation assay,and migration ability was evaluated via a wound-healing assay.Epidermal growth factor receptor(EGFR)/MAPK pathway proteins were tested via immunoblotting.EGFR localization was examined by immunofluorescence assay.RESULTS:YM155 suppressed ARPE-19 cells’viability in a time and concentration-dependent manner.A high dose of YM155 caused a small amount of ARPE-19 cell death.YM155 significantly diminished the ARPE-19 cells’proliferative and migrative capacity.YM155 downregulated total EGFR and phosphorylated external signalregulated protein kinase(ERK),and it up-regulated the phosphorylation of P38 MAPK and c-Jun N-terminal kinase(JNK).YM155 induced endocytosis of EGFR in ARPE-19 cell.YM155 also attenuated EGF-induced ARPE-19 cells’proliferative and migrative capacity.Moreover,YM155 significantly decreased the expression of phosphorylated EGFR and ERK after treated by EGF.CONCLUSION:YM155 inhibits RPE cell survival,the cell proliferative and migrative capacity,and it effectuates a small amount of cell death through the EGFR/MAPK signaling pathway.YM155 might,therefore,be an agent to prevent and treat abnormal RPE cell survival in proliferative vitreoretinopathy.展开更多
Background: Neuroblastoma exhibits a high incidence of chromosomal translocations, the most common being the gain of a portion of the long arm of chromosome 17. This region includes the gene BIRC5/survivin, which is h...Background: Neuroblastoma exhibits a high incidence of chromosomal translocations, the most common being the gain of a portion of the long arm of chromosome 17. This region includes the gene BIRC5/survivin, which is highly upregulated in neuroblastoma and correlates with poor prognosis. Survivin is a member of the inhibitor of apoptosis family of proteins and is involved in tumor cell survival and migration. YM155 is a small molecule inhibitor of survivin transcription and has shown efficacy in several cancer model systems both?in vitro?and?in vivo. Procedure: Cells were treated with YM155 and effects on migration, invasion, and apoptosis signaling were investigated?in vitro. Tumor burden was assessed in xenografted mice by measuring tumor volume and liver metastases. Results: Treatment with YM155 caused a dose-dependent decrease in survivin expression and induction of apoptosis. Lower concentrations of YM155 reduced cell migration and invasion by 15% - 50% which varied by cell line. In a xenograft model, YM155 treatment inhibited tumor growth by 25% - 70%, reduced metastatic burden in the liver by 50%, and prolonged animal survival. Conclusion: The data suggest YM155 as a possible therapeutic agent for metastatic neuroblastoma.展开更多
基金Supported by the Natural Science Foundation of Shaanxi Province,China(No.2018JM7040)the Science and Technology Planned Projects of Xi’an City,China[No.20YXXJ008(4)]the Health Research Personnel Training Project of Xi’an Health Commission,China(No.J201901009)。
文摘AIM:To investigate YM155’s effect on retinal pigment epithelium(RPE)cells’viability and the potential regulatory mechanisms.METHODS:Human immortalized RPE cell lines(ARPE-19 cell line)were processed with YM155 and epidermal growth factor(EGF).ARPE-19 cell viability was detected by methyl thiazolyl tetrazolium assay,and apoptosis was tested by flow cytometry assay.ARPE-19 cell proliferation was assessed with bromodeoxyuridine tagged incorporation assay,and migration ability was evaluated via a wound-healing assay.Epidermal growth factor receptor(EGFR)/MAPK pathway proteins were tested via immunoblotting.EGFR localization was examined by immunofluorescence assay.RESULTS:YM155 suppressed ARPE-19 cells’viability in a time and concentration-dependent manner.A high dose of YM155 caused a small amount of ARPE-19 cell death.YM155 significantly diminished the ARPE-19 cells’proliferative and migrative capacity.YM155 downregulated total EGFR and phosphorylated external signalregulated protein kinase(ERK),and it up-regulated the phosphorylation of P38 MAPK and c-Jun N-terminal kinase(JNK).YM155 induced endocytosis of EGFR in ARPE-19 cell.YM155 also attenuated EGF-induced ARPE-19 cells’proliferative and migrative capacity.Moreover,YM155 significantly decreased the expression of phosphorylated EGFR and ERK after treated by EGF.CONCLUSION:YM155 inhibits RPE cell survival,the cell proliferative and migrative capacity,and it effectuates a small amount of cell death through the EGFR/MAPK signaling pathway.YM155 might,therefore,be an agent to prevent and treat abnormal RPE cell survival in proliferative vitreoretinopathy.
文摘Background: Neuroblastoma exhibits a high incidence of chromosomal translocations, the most common being the gain of a portion of the long arm of chromosome 17. This region includes the gene BIRC5/survivin, which is highly upregulated in neuroblastoma and correlates with poor prognosis. Survivin is a member of the inhibitor of apoptosis family of proteins and is involved in tumor cell survival and migration. YM155 is a small molecule inhibitor of survivin transcription and has shown efficacy in several cancer model systems both?in vitro?and?in vivo. Procedure: Cells were treated with YM155 and effects on migration, invasion, and apoptosis signaling were investigated?in vitro. Tumor burden was assessed in xenografted mice by measuring tumor volume and liver metastases. Results: Treatment with YM155 caused a dose-dependent decrease in survivin expression and induction of apoptosis. Lower concentrations of YM155 reduced cell migration and invasion by 15% - 50% which varied by cell line. In a xenograft model, YM155 treatment inhibited tumor growth by 25% - 70%, reduced metastatic burden in the liver by 50%, and prolonged animal survival. Conclusion: The data suggest YM155 as a possible therapeutic agent for metastatic neuroblastoma.
