title: [Inhibitory effect of folic acid/polyamide-amine as a miR-7 vector on the growth of glioma in mice].
abstract: OBJECTIVE
  To explore if folic acid/polyamide-amine (FA/PAMAM) enhances the therapeutic effect of miR-7gene therapy for glioma in vivo.
  
  
  METHODS
  The miR-7 gene was transfected into U251 glioma cells by FA/PAMAM. The efficiency of gene transfection was assessed by fluorescence microscopy. The miR-7 level was detect by quantitative RT-PCR. Intracranial glioma models were established in thymectomized mice, and FA/PAMAM nanoparticles were transplanted into the tumors in situ 3 days later. The animal survival was recorded and the gross tumor volume and degree of edema were observed by MRI. Apoptosis in the glioma cells and expression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) were assessed by immunohistochemistry, and EGFR and AKT-2 protein expression was detected by Western blot assay.
  
  
  RESULTS
  Compared with the liposomes, the FA/PAMAM nanoparticles were more efficient to transfer miR-7 gene into U251 glioma cells, MRI showed that the tumor growth was much slower in the FA/PAMAM/miR-7 group, and the animal survival time was longer. The apoptosis rate was (5.3 ± 0.9)% in the control group, (11.4 ± 2.4)% in the liposome/miR-7 group, and (17.7 ± 3.7)% in the FA/PAMAM/miR-7 group. The immunohistochemical assay showed that the levels of PCNA, MMP-2 and MMP-9 protein in the FA/PAMAM/miR-7 group were (34.6 ± 5.4)%, (24.5 ± 4.1)%, (25.4 ± 5.1)%, respectively, significantly lower than those in the liposome/miR-7 group (49.3 ± 5.9)%, (31.7 ± 7.1)% and (39.4 ± 6.4)%, respectively, and those in the control group (57.3 ± 7.4)%, (45.4 ± 6.9)% and (55.1 ± 7.3)%, respectively (all P < 0.05). The expressions of EGFR and AKT-2 proteins were 1.09 ± 0.12 and 0.62 ± 0.10 in the control group, 0.63 ± 0.11 and 0.43 ± 0.07 in the liposome/miR-7 group, and significantly deceased (0.47 ± 0.09 and 0.31 ± 0.04, respectively) in the FA/PAMAM/miR-7 group (all P < 0.05).
  
  
  CONCLUSIONS
  Compared with the liposomes, FA/PAMAM can transfect miR-7 into glioma cells with a higher efficiency in vivo, makes a longer time of the drug action, and shows a certain inhibitory effect on the growth of glioma, therefore, might become a new drug targeting agent in gene therapy forglioma.
authors.affiliation: Department of Neurosurgery, the Fifth Central Hospital of Tianjin, Tianjin, China.
authors.forename: Xiao-zhi
authors.initials: XZ
authors.lastname: Liu
authors.forename: Zhi-guo
authors.initials: ZG
authors.lastname: Su
authors.forename: Zhong-min
authors.initials: ZM
authors.lastname: Jiang
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Song
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Zhen-lin
authors.initials: ZL
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry; D066246:ErbB Receptors / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D053758:Nanoparticles; D009368:Neoplasm Transplantation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013934:Thymectomy; D014162:Transfection
chemical_list: D050091:Dendrimers; D066246:ErbB Receptors; D005492:Folic Acid; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D035683:MicroRNAs; D018809:Proliferating Cell Nuclear Antigen; D051057:Proto-Oncogene Proteins c-akt; C549242:MIRN7-1 microRNA, human; C104700:PAMAM Starburst; C512478:EGFR protein, human; C494921:AKT2 protein, human