Abstract

We investigated whether IFN-β inhibits the growth of human malignant glioma and induces glioma cell apoptosis using the human IFN-β gene transfected into glioma cells. A eukaryonic expression vector (pSV2IFNβ) for IFN-β was transfected into the glioma cell line SHG44 using liposome transfection. Stable transfection and IFN-β expression were confirmed using an enzyme-linked immunosorbent assay (ELISA). Cell apoptosis was also assessed by Hoechst staining and electron microscopy. In vivo experiments were used to establish a SHG44 glioma model in nude mice. Liposomes containing the human IFN-β gene were injected into the SHG44 glioma of nude mice to observe glioma growth and calculate tumor size. Fas expression was evaluated using immunohistochemistry. The IFN-β gene was successfully transfected and expressed in the SHG44 glioma cells in vitro. A significant difference in the number of apoptotic cells was observed between transfected and non- transfected cells. Glioma growth in nude mice was inhibited in vivo, with significant induction of apoptosis. Fas expression was also elevated. The IFN-β gene induces apoptosis in glioma cells, possibly through upregulation of Fas. The IFN-β gene modulation in the Fas pathway and apoptosis in glioma cells may be important for the treatment of gliomas.

Highlights

  • At present, there is no effective treatment for patients with malignant and recurrent glioma

  • We investigated whether IFN-β inhibits the growth of human malignant glioma and induces glioma cell apoptosis using the human IFN-β gene transfected into glioma cells

  • Liposomes containing the human IFN-β gene were injected into the SHG44 glioma of nude mice to observe glioma growth and calculate tumor size

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Summary

Introduction

There is no effective treatment for patients with malignant and recurrent glioma. Patients with malignant glioma have very poor prognosis, even with surgical resection, radiation, and chemotherapy. Gene therapy has received particular attention as a promising treatment for malignant glioma. IFNs are a family of natural glycoproteins that consist of IFN-α, β, and γ. The antiviral activity of IFNs led to their discovery. Later data revealed that they control cell growth and differentiation (Hertzog et al, 1994), inhibit oncogene expression, and activate T lymphocytes, natural killer cells, and macrophages. Interferon inhibits the growth of tumor blood vessels and cellular immunity activation (Nakahara et al, 2003; Konjević et al, 2010; Williams et al, 2010)

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