Antitumor activity of combined endostatin and thymidine kinase gene therapy in C6 glioma models
| Autor: | Zhaohui Ni, Honglan Huang, Fengbo Su, Wenming Guan, Yan Chen, Shijun Yan, Chunshan Yao |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Programmed cell death animal structures viruses Genetic enhancement Genetic Vectors Gene Expression endostatin (ES) Thymidine Kinase 03 medical and health sciences 0302 clinical medicine Cell Movement Transduction Genetic tumor inhibition Cell Line Tumor Glioma medicine Animals Radiology Nuclear Medicine and imaging Ganciclovir Cell Proliferation Original Research Cancer Biology Chemistry Cell growth thymidine kinase (TK) fungi Genes Transgenic Suicide Genetic Therapy C6 glioma Transfection medicine.disease Xenograft Model Antitumor Assays Endostatins Rats Tumor Burden Disease Models Animal 030104 developmental biology Oncology Apoptosis Thymidine kinase 030220 oncology & carcinogenesis Cancer research Endostatin |
| Zdroj: | Cancer Medicine |
| ISSN: | 2045-7634 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |