title: Potent effects of dioscin against pancreatic cancer via miR-149-3P-mediated inhibition of the Akt1 signalling pathway.
abstract: The aim of the present study was to investigate the effects and possible underlying mechanisms of dioscin against pancreatic cancer in vitro and in vivo.
  
  
  
  In vitro actions of dioscin on viability of ASPC-1 and PANC-1 cells, and in vivo effects to suppress the tumour growth of cell xenografts in nude mice were assessed. In addition, microRNA microarray analysis determined which microRNAs were affected by dioscin. The mechanisms underlying the actions of dioscin against pancreatic cancer were elucidated in terms of Akt1 and other proteins related to aopoptosis.
  
  
  
  Dioscin markedly induced apoptosis and significantly suppressed the tumour growth of ASPC-1 and PANC-1 cell xenografts, in nude mice. Total of 107 microRNAs with differential changes were found, in which miR-149-3P targeted with Akt1 was markedly up-regulated by dioscin. Further studies showed that dioscin significantly down-regulated Akt1 levels, and thus induced cell apoptosis by increasing the levels of Bax, Apaf-1, cleaved caspase-3/9, cleaved PARP, suppressing Bcl-2 levels, and causing cytochrome c release. The effects of an inhibitor of miR-149-3P and of siRNA of testicular Akt1 suggested that dioscin showed excellent activity against pancreatic cancer via miR- 149-3P-mediated inhibition of Akt1 signalling pathway.
  
  
  
  Collectively, these findings confirmed the potent effects of dioscin against pancreatic cancer and also provided novel insights into the mechanisms of the compound as a potential candidate for the treatment of pancreatic cancer.
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Si
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, China.
authors.forename: Lianhong
authors.initials: L
authors.lastname: Yin
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, China.
authors.forename: Youwei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, China.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; C551557:MIRN149 microRNA, human; D035683:MicroRNAs; C019357:dioscin; D051057:Proto-Oncogene Proteins c-akt; D004144:Diosgenin