Effects of gamma-interferon gene on brain gliomas and survival of tumor-carrying rats

Xuefeng WANG; Haiquan TAO; Xiaoqian LIU; Fuming YANG

ABSTRACT

BACKGROUND:

It has become a hot issue to treat malignant tumors with retroviral mediated cytokines. But it remains a controversy whether retroviral mediated γ-interferon(IFN-γ) is valid in killing glioma cells and prolonging the survival of tumor carriers.

OBJECTIVE:

To observe the effect of retrovital mediated γ-interferon on the growth of glioma and the survival of tumor-carrying rats.

DESIGN:

Completely ramdomized trial based on animals.

SETTING:

Neurosurgery department of a hospital affiliated to a university.MATERIALS The trial was conducted in the Neurosurgery Institute of Harbin Medical Unicersity from July 2002 to July 2004. The subjects were 60 male Wistar rats provided by the Animal Center of the First Affiliated Hospital of Harbin Medical Unicersity. They were randomly assigned into 3groups C6 control group, C6/PA317neo control group and C6/PA317IFN-γ treatment group, 20 in each group.

INTERVENTIONS:

Retroviral vector containing murine IFN-γ gene was transferred into retroviral package cell PA317. A high titer PA317IFN-γ cell line was obtained after G418 resistance screening. In the right basal ganglion area 1 × 106 C6 cells was injected in each of the rats. The rats in C6groups received no more intervention. Those in C6/PA317neo control group received injection of 1 × 106 PA317IFN-γ cells in the right basal ganglion 4days after C6 injection. Those in C6/PA317IFN-γ treatment group received injection of 1 × 106 PA317IFN-γ cells in the right basal ganglion 4 days after selected from each group to be kill, and the brains were taken out to make frozen sections for SABC immunohistochemical staining. The CD4 and CD8 T was measured with imaging processing software under microscope.

RESULTS:

The mean survival time of rats in C6 and C6/PA317neo control groups was(27.10 ± 0.82) days and (26.60 ± 0.93) days respectively( P ＞ 0.05), while that in treatment group was(49.30 ± 4. 17) days and there were five rats outlived beyond 60 days( P ＜ 0.01 vs the two controls). The tumor volume in the two control groups was of no difference but the tumor volume in treatment was significantly smaller than that in control groups( P ＜ 0. 01 ) . The CD4 and CD8 lymphocytes infiltration in treatment group was more than that in control groups( P ＜ 0.01) and there was no difference between the two controls( P ＞ 0.05) . It was also revealed through immunohistochemical examination that in treatment group there was Brdu positive cells on the 7th day and they disappeared on the 16th day. But there was no Brdu positive cells in the control groups.

CONCLUSION:

Intratumor injection of PA317IFN-γ induces anti-tumor immunal reaction in rats. Retroviral mediated IFN-γ inhibits tumor growth and prolongs rat survival.