Open AccessAntitumor activity of combined endostatin and thymidine kinase gene therapy in C6 glioma models
Author(s) -
Chen Yan,
Huang Honglan,
Yao Chunshan,
Su Fengbo,
Guan Wenming,
Yan Shijun,
Ni Zhaohui
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.798
Subject(s) - internal ribosome entry site , thymidine kinase , genetic enhancement , transfection , cancer research , glioma , suicide gene , apoptosis , medicine , cell culture , microbiology and biotechnology , herpes simplex virus , biology , immunology , gene , virus , messenger rna , translation (biology) , biochemistry , genetics
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 ( HUVEC s) ECV 304 and C6 rat glioma cell line. Ganciclovir ( GCV ) was used to induce cell death in transfected C6 cells. We found that ECV 304 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.