Enhanced anti-tumor activity by adenovirus mediated LIF and IL-24 co-expression on glioma cells and its mechanism

Main Article Content

Yaodong Zhao
Zilong Wei
Jia Yin
Quanbin Zhang
Yunbo Shan
Weihua Sheng
Jicheng Yang

Keywords

gene therapy, bicistronic adenovirus, LIF, IL-24, glioma

Abstract

Objective: Gene therapy on the glioma has been studied for many years, but most studies still remain at the level of single gene therapy. However, the glioma is characterized by a multistep process of genetic and molecular changes to oncogenes and tumor suppressor genes, which limits the efficacy of single gene-mediated therapy due to the difficulty of finding a pivotal gene conferring its occurrence in glioma gene therapy. In this paper, we try to study the anti-tumor effects and mechanism of a recombinant adenoviral vector co-expressing leukemia inhibitory factor (LIF) and interleukin-24 (IL-24) on glioma cells. Materials and Methods: LIF/IL-24 bicistronic adenovirus (Ad-LIF-IL-24) was constructed and preserved by our laboratory. The enhanced growth-suppressing and apoptosis-inducing effect of Ad-LIF-IL-24 on the U251 glioma cells in vitro was assessed, and the expressions of the apoptosis-related genes (bcl-2, bax, and ICE) were determined. Results: Ad-LIF-IL-24 could induce much more cellular apoptosis of U251 glioma cells than either Ad-LIF or Ad-IL-24 alone at the same virus titer. Molecularly, Ad-LIF-IL-24 could significantly enhance the expressions of bax and ICE though it inhibits the expression of bcl-2. Conclusion: Cancer gene therapy combining LIF and IL-24 may constitute a novel and more effective therapeutic strategy for gliomas, with good potential prospects of clinical application.
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