title: Antitumor activity of combined endostatin and thymidine kinase gene therapy in C6 glioma models.
abstract: The combination of Endostatin (ES) and Herpes Simplex Virus thymidine kinase (HSV-TK) gene therapy is known to have antitumor activity in bladder cancer. The potential effect of ES and TK therapy in glioma has not yet been investigated. In this study, pTK-internal ribosome entry site (IRES), pIRES-ES, and pTK-IRES-ES plasmids were constructed; pIRES empty vector served as the negative control. The recombinant constructs were transfected into human umbilical vein endothelial cells (HUVECs) ECV304 and C6 rat glioma cell line. Ganciclovir (GCV) was used to induce cell death in transfected C6 cells. We found that ECV304 cells expressing either ES or TK-ES showed reduced proliferation, decreased migration capacity, and increased apoptosis, as compared to untransfected cells or controls. pTK-IRES-ES/GCV or pTK-IRES/GCV significantly suppressed cell proliferation and induced cell apoptosis in C6 cells, as compared to the control. In addition, the administration of pIRES-ES, pTK-IRES/GCV, or pTK-IRES-ES/GCV therapy improved animal activity and behavior; was associated with prolonged animal survival, and a lower microvessel density (MVD) value in tumor tissues of C6 glioma rats. In comparison to others, dual gene therapy in form of pTK-IRES-ES/GCV had a significant antitumor activity against C6 glioma. These findings indicate combined TK and ES gene therapy was associated with a superior antitumor efficacy as compared to single gene therapy in C6 glioma.
authors.affiliation: Department of Neurosurgery, The Second Hospital of Jilin University, Changchun, Jilin, 130021, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathogenobiology, College of Basic Medical Science, Jilin University, Changchun, Jilin, 130021, P. R. China.
authors.forename: Honglan
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, The Second Hospital of Jilin University, Changchun, Jilin, 130021, P. R. China.
authors.forename: Chunshan
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, The Second Hospital of Jilin University, Changchun, Jilin, 130021, P. R. China.
authors.forename: Fengbo
authors.initials: F
authors.lastname: Su
authors.affiliation: Department of Neurosurgery, The Second Hospital of Jilin University, Changchun, Jilin, 130021, P. R. China.
authors.forename: Wenming
authors.initials: W
authors.lastname: Guan
authors.affiliation: Department of Neurosurgery, The Second Hospital of Jilin University, Changchun, Jilin, 130021, P. R. China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Yan
authors.affiliation: Department of Pathogenobiology, College of Basic Medical Science, Jilin University, Changchun, Jilin, 130021, P. R. China. nich@jlu.edu.cn.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Ni
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D043169:Endostatins / Q000235:genetics*; D015774:Ganciclovir / Q000494:pharmacology; D015870:Gene Expression; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D051381:Rats; D013937:Thymidine Kinase / Q000235:genetics*; D014161:Transduction, Genetic; D047368:Tumor Burden / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D043169:Endostatins; D013937:Thymidine Kinase; D015774:Ganciclovir
keywords: C6 glioma; Ganciclovir; endostatin (ES); thymidine kinase (TK); tumor inhibition