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摘要:Ovarian cancer(OC) is a leading cause of female mortality.OC may be treated with surgery,chemotherapy and/or radiation therapy.However,OC develops resistance to current platinum-and taxane-based therapy.Plant extracts have been shown to block tumor progression.Previously we have shown Emblica officinalis(Amla extract-AE) has anti-neoplastic effect on OC cells both in vitro and in vivo.We hypothesize that AE inhibits growth of OC through microRNA(miR)-regulated anti-angiogenic mechanism(s).OC cells OVCAR3 and SKOV3 were used.Anti-proliferative effects of AE on OC cells in vitro were studied using MTT and LDH assays.Effect of AE on endothelial cells and expression of angiogenic genes after AE treatment was studied in OC cells using gene array.Effect of AE on migration and invasion and expression of OC related miRNAs,proangiogenic receptor IGFIR and angiogenic marker CD31 were studied.Expression of miR-375 in exosomes released from OC cells was studied.Expression of metastasis-associated transcription factor,SNAILl and adhesion protein,E-cadherin in OC cells and OC cells derived tumor after AE treatment was studied.Our results showed inhibitory effect of AE on proliferation,migration and invasiveness(0.001≥P)of OC cells.AE reduced the expression of several angiogenic genes,with maximum effect on hypoxia-inducible factor 1 alpha in OC cells.AE induced the expression of miR-375 in OC cells that was blocked by an exogenous miR-375 inhibitor(0.001≥P).AE decreased IGFIR,a target of miR-375,gene and protein expression(0.001≥P).AE decreased SNAILl(0.002≥P) and increased E-cadherin(0.001≥P) protein expression in OC cells.AE increased miR-375 associated exosomes in OC cells medium(0.01≥P).AE caused >90%regression of tumor growth and inhibited the expression of IGF1 R,SNAIL1,CD31 proteins and increased E-cadherin protein expression in OC cells-derived xenograft tumor in nude mice.These results suggest that AE modulates cancer cells and the tumor microenvironment via activation of miR-375 and by targeting IGFIR and SNAILl in OC cells.AE also significantly reduced the expression of several angiogenic genes,including hypoxia-inducible factor 1 alpha in OC cells.These results suggest that AE decreases angiogenesis in OC through modulation of multiple targets.
会议名称:

BIT’s 10th Annual World Cancer Congress-2017

会议时间:

2017-05-19

会议地点:

Barcelona, Spain

  • 专辑:

    医药卫生

  • 专题:

    妇产科学; 肿瘤学

  • 分类号:

    R737.31

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