Expression of antisense bcl-2 cDNA abolishes tumorigenicity and enhances chemosensitivity of human malignant glioma cells

✍ Scribed by Cong Ju Zhu; Yong Biao Li; Meng Cheong Wong

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 209 KB
• Volume: 74
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.10722

✦ Synopsis

Abstract

Bcl‐2 is a key antiapoptotic protein, and it confers survival advantages on many types of tumors by inhibiting apoptotic cell death. Malignant gliomas are the most common primary central nervous system tumors, but the role of bcl‐2 in these tumors has not been defined. We investigated the impact of bcl‐2 on malignant gliomas by suppressing its expression. Antisense human bcl‐2 cDNA was transfected into human malignant glioma cells. The effects of bcl‐2 protein down‐regulation on glioma cell morphology, in vitro tumor growth, and tumorigenicity in nude mice, as well as chemosensitivity to cisplatin, were studied. Expression of antisense bcl‐2 cDNA decreased bcl‐2 protein by more than sixfold. Antisense bcl‐2 stable transfectants (AS‐bcl‐2) showed profound morphological change and markedly retarded cell growth in vitro. Transplantation of AS‐bcl‐2 cells resulted in no tumor formation, whereas backbone plasmid transfectant control formed tumors in each mouse transplanted. Expression of antisense bcl‐2 in glioma cells resulted in significantly increased cytotoxicity of cisplatin. In conclusion, antisense bcl‐2 expression can effectively reduce glioma survival, including retarding in vitro growth, complete loss of tumorigenicity, and significantly enhanced cisplatin cytotoxicity. These results suggest that bcl‐2 plays an important role in glioma malignancy and chemoresistance. Development of strategies targeted at bcl‐2 has the potential to advance treatment for malignant gliomas. © 2003 Wiley‐Liss, Inc.