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.


Interferon-${\beta}$;human malignant glioma;apoptosis;therapy


  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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