Induction of Apoptosis in Glioma Cells and Upregulation of Fas Expression Using the Human Interferon-β Gene

  • Guo, Yan (Department of Neurosurgery, the 6th Hospital Affiliated to Shanghai Jiaotong University) ;
  • Wang, Gan (Department of Neurosurgery, the 6th Hospital Affiliated to Shanghai Jiaotong University) ;
  • Gao, Wen-Wei (Department of Neurosurgery, the 6th Hospital Affiliated to Shanghai Jiaotong University) ;
  • Cheng, Shi-Wen (Department of Neurosurgery, the 6th Hospital Affiliated to Shanghai Jiaotong University) ;
  • Wang, Ren (Department of Neurosurgery, the 6th Hospital Affiliated to Shanghai Jiaotong University) ;
  • Ju, Shi-Ming (Department of Neurosurgery, the 6th Hospital Affiliated to Shanghai Jiaotong University) ;
  • Cao, He-Li (Department of Neurosurgery, the 6th Hospital Affiliated to Shanghai Jiaotong University) ;
  • Tian, Heng-Li (Department of Neurosurgery, the 6th Hospital Affiliated to Shanghai Jiaotong University)
  • Published : 2012.06.30


We investigated whether IFN-${\beta}$ inhibits the growth of human malignant glioma and induces glioma cell apoptosis using the human IFN-${\beta}$ gene transfected into glioma cells. A eukaryonic expression vector ($pSV2IFN{\beta}$) for IFN-${\beta}$ was transfected into the glioma cell line SHG44 using liposome transfection. Stable transfection and IFN-${\beta}$ 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-${\beta}$ 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-${\beta}$ 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-${\beta}$ gene induces apoptosis in glioma cells, possibly through upregulation of Fas. The IFN-${\beta}$ gene modulation in the Fas pathway and apoptosis in glioma cells may be important for the treatment of gliomas.


  1. Buechner SA, Wernli M, Harr T, et al (1997). Regression of basal cell carcinoma by intralesional interferon-alpha treatment is mediated by CD95 (Apo-1/Fas)-CD95 ligand-induced suicide. J Clin Invest, 100, 2691-6.
  2. Dinney CP, Bielenberg DR, Perrotte P, et al (1998). Inhibition of basic fibroblast growth factor expression, angiogenesis, and growth of human bladder carcinoma in mice by mice by systemic interferon-a administration. Cancer Res, 58, 808-14.
  3. Fabra A, Nakajima M, Bucana CD, Fidler IJ (1992). Modulation of the invasive phenotype of human colon carcinoma cells by organ-specific fibroblasts of nude mice. Differentiation, 52, 101-10.
  4. Gohji K, Fidler IJ, Tsan R, et al (1994). Human recombinant interferons-b and g decrease gelatinase production and invasion by human KG-2 renal carcinoma cells. Int J Cancer, 58, 380-4.
  5. Hertzog PJ, Hwang SY, Kola I (1994). Role of interferons in the regulation of cell proliferation, differentiation, and development. Mol Reprod Dev, 39, 226-32.
  6. Ito S, Natsume A, Shimato S, et al (2010). Human neural stem cells transduced with IFN-beta and cytosine deaminase genes intensify bystander effect in experimental glioma. Cancer Gene Ther, 17, 299-306.
  7. Kageshita T, Mizuno M, Ono T, et al (2001). Growth inhibition of human malignant melanoma transfected with the human interferon-beta gene by means of cationic liposomes. Melanoma Res, 11, 337-42.
  8. Konjevic G, Mirjacic Martinovic K, Vuletic A, Babovic N (2010). In-vitro IL-2 or IFN-${\alpha}$-induced NKG2D and CD161 NK cell receptor expression indicates novel aspects of NK cell activation in metastatic melanoma patients. Melanoma Res, 20, 459-67.
  9. Koshiji M, Adachi Y, Sogo S, et al (1998). Apoptosis of colorectal adenocarcinoma (COLO 201) by tumour necrosis factor-alpha (TNF-alpha) and/or interferon-gamma (IFN-gamma), resulting from down-modulation of Bcl-2 expression. Clin Exp Immunol, 111, 211-8.
  10. Lin W, Zhang X, Wang ZX, et al (2004). Growth inhibition of glioma cell line SHG44 by transfection of human interferon-beta gene liposome. Chin J Neurosurg Dis Res, 3, 226-9.
  11. Mizuno M, Yoshida J, Sugita K, et al (1990). Growth inhibition of glioma cells transfected with the human beta-interferon gene by liposomes coupled with a monoclonal antibody. Cancer Res, 50, 7826-9.
  12. Nakahara N, Pollack IF, Storkus WJ, et al (2003). Effective induction of antiglioma cytotoxic T cells by coadministration of interferon-beta gene vector and dendritic cells. Cancer Gene Ther, 10, 549-58.
  13. Oliveira IC, Sciavolino PJ, Lee TH (1992). Down regulation of interleukin 8 gene expression in human fibroblasts, unique mechanism of transcriptional inhibition by interferon. Natl Acad Sci USA, 89, 9049-53.
  14. Sangfelt O, Erickson S, Castro J, et al (1997). Induction of apoptosis and inhibition of cell growth are independent responses to interferon-alpha in hematopoietic cell lines. Cell Growth Differ, 8, 343-52.
  15. Singh RK, Gutman M, Bucana CD, et al (1995). Interferons alpha and beta down regulate the expression of basic fibroblast growth factor in human carcinomas. Proc Natl Acad, 92, 4562-6.
  16. Wakabayashi T, Kajita Y, Hatano N, et al (2000). Clinicopathological study of oligodendroglial tumors, the effectiveness of interferon beta, ACNU/MCNU, and radiation (IAR/IMR) for anaplastic tumors. Brain Tumor Pathol, 17, 29-33.
  17. Williams RF, Myers AL, Sims TL, Ng CY, Nathwani AC, Davidoff AM (2010). Targeting multiple angiogenic pathways for the treatment of neuroblastoma. J Pediatr Surg, 45, 1103-9.
  18. Yoshida J, Mizuno M, Wakabayashi T (2004). Interferon-beta gene therapy for cancer, basic research to clinical application. Cancer Sci, 95, 858-65.

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