Minicircle-IFNγ induces antiproliferative and antitumoral effects in human nasopharyngeal carcinoma

Purpose: The aims of this work were to investigate the antitumor effect of IFN gamma gene transfer on human nasopharyngeal carcinoma (NPC) and to assess the potential of minicircle vector for antitumor gene therapy. Experimental Design: We developed a recombinant minicircle vector carrying the human IFN gamma gene and evaluated the effects of minicircle-mediated IFN gamma gene transfer on NPC cell lines in vitro and on xenografts in vivo. Results: Relative to p2 Phi C31-IFN gamma, minicircle-mediated IFN gamma gene transfer in vitro resulted in 19- to 102-fold greater IFN gamma expression levels in transfected cells (293, NIH 3T3, CNE-1, CNE-2, and C666-1) and inhibited the growth of CNE-1, CNE-2, and C666-1 cells more efficiently, reducing relative growth rates to 7.1 +/- 1.6%, 2.7 +/- 1.0%, and 6.1 +/- 1.6%, respectively. Flow cytometry and caspase-3 activity assays suggested that the antiproliferative effects of IFN gamma gene transfer on NPC cell lines could be attributed to GO-G, arrest and apoptosis. Minicircle-mediated intra-tumoral IFN gamma expression in vivo was 11 to 14 times higher than p2 Phi C31-IFN gamma in CNE-2- and C666-1-xenografted mice and lasted for 21 days. Compared with p2 Phi C31-IFN gamma treatment, minicircle-IFN gamma treatment significantly increased survival and achieved inhibition rates of 77.5% and 83%, respectively. Conclusions: Our data indicate that IFN gamma gene transfer exerts antiproliferative effects on NPC cells in vitro and leads to a profound antitumor effect in vivo. Minicircle-IFN gamma is more efficient than corresponding conventional plasmids due to its capability of mediating long-lasting high levels of IFN gamma gene expression. Therefore, minicircle-mediated IFN gamma gene transfer is a promising novel approach in the treatment of NPC.