title: Lentivirus-mediated CD/TK fusion gene transfection neural stem cell therapy for C6 glioblastoma.
abstract: A suicide gene can convert nontoxic prodrugs into toxic products to kill tumor cells. In this study, our aim was to transfect lentivirus-mediated CD/TK fusion gene into Wistar rat's neural stem cells (NSC) and then implant the NSC into a C6 glioma model to observe a C6 glioma growth inhibition effect. Primary NSC and stable transfection CD/TK fusion gene cell lines were established. To observe the tumor size and rat survival period in different groups, C6 glioma cell apoptosis and cell viability rate were applied to analyze the tumor inhibition effect of the neural stem cells' transfected CD/TK fusion gene. C6 cell viability showed that CDglyTK-NSC + GCV/5-Fc (group 1) was lower than CDglyTK-NSC (group 2), NSC + GCV/5-Fc (group 3), and control (group 4) from day 2 (p < 0.05), and the apoptosis rate was higher in group 1 compared with that of other groups (50.6%, p < 0.05) either in vitro or in vivo (35.47%, p < 0.05); both cell viability and apoptosis had no significance in the other three groups. In vivo, tumor size in group 1 was 7.76 ± 1.37 mm(3), which is smaller than the others (group2 27.28 ± 4.11 mm(3), group3 27.94 ± 2.08 and 28.61 ± 2.97 mm(3); p < 0.05). The other groups' tumor size was not significant (p > 0.05). Survival time of rats treated with CDglyTK-NSC + GCV/5-Fc (group 1) was significantly longer than that of the other groups (p < 0.05; group 1 48.86 ± 1.97, group 2 28.67 ± 3.75, group 3 31.5 ± 1.27, group 4 29.3 ± 1.33). We also showed that the transfected C6 cells had a migratory capacity toward gliomas in vivo. Transfected CD/TK fusion gene neural stem cells combined with propyl-guanosine and 5-flucytosine double prodrug significantly inhibit the development of glioma.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, No. 148 Health Road, Nangang District, Harbin, Heilongjiang, 150000, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Niu
authors.forename: Chunyang
authors.initials: C
authors.lastname: Xing
authors.forename: Chao
authors.initials: C
authors.lastname: Yan
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Yuqiong
authors.initials: Y
authors.lastname: Cui
authors.forename: Haisheng
authors.initials: H
authors.lastname: Peng
authors.forename: Yingli
authors.initials: Y
authors.lastname: Chen
authors.forename: Dianjun
authors.initials: D
authors.lastname: Li
authors.forename: Chuanlu
authors.initials: C
authors.lastname: Jiang
authors.forename: Nannan
authors.initials: N
authors.lastname: Li
authors.forename: Haicheng
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005437:Flucytosine / Q000008:administration & dosage / Q000494:pharmacology; D015774:Ganciclovir / Q000008:administration & dosage / Q000494:pharmacology; D005822:Genetic Vectors / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D016086:Lentivirus / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics
chemical_list: D000963:Antimetabolites; D000998:Antiviral Agents; D011993:Recombinant Fusion Proteins; D005437:Flucytosine; D013937:Thymidine Kinase; D043525:Cytosine Deaminase; D015774:Ganciclovir