Synergistic antitumor effect of ING4/PTEN double tumor suppressors mediated by adenovirus modified with RGD on glioma.

BACKGROUND: Gene therapy is regarded as a new and promising therapeutic modality for cancers, and adenovirus is one of the most frequently used vectors. However, because of low or absent coxsackievirus and adenovirus receptor levels on the surface of many kinds of tumor cells, the efficiency of adenovirus infection of target tumor cells may be low. Meanwhile, gene therapy by a single vector carrying two or more anti-oncogenes can improve treatment effects and reduce side effects from vectors. In this research, we aimed to detect the anti-tumor effect of ING4/PTEN double tumor suppressors mediated by adenovirus modified with arginine(R)-glycine(G)-aspartate(D) (RGD) on glioma cells.

METHODS: We treated U87 glioma cells with PBS, blank adenovirus or adenovirus carrying RGD, ING4, PTEN, or both ING4 and PTEN, then we detected and compared the U87 cells' growth, apoptosis, and invasion. Moreover, we established a U87 glioma transplantation tumor model to study the anti-tumor effect in vivo by measuring the volume and weight of tumor masses in each condition. In addition, we analyzed the transcription of related genes by fluorescent quantitative PCR and detected their expression by immunohistochemistry staining to reveal the underlying mechanisms.

RESULTS: The double tumor suppressors ING4/PTEN could inhibit the growth of U87 glioma cells with a synergistic antitumor effect, and the RGD modification also acted as an anti-oncogene to inhibit U87 cell invasion and tumor angiogenesis.

CONCLUSIONS: The ING4/PTEN double tumor suppressors mediated by adenovirus modified with RGD had a significantly synergistic antitumor effect on glioma.