Minicircle-IFNγ Induces Antiproliferative and Antitumoral Effects in Human Nasopharyngeal Carcinoma

• Published in: Clinical cancer research Vol. 12; no. 15; pp. 4702 - 4713
• Main Authors: Wu, Jiangxue, Xiao, Xia, Zhao, Peng, Xue, Gang, Zhu, Yinghui, Zhu, Xiaofeng, Zheng, Limin, Zeng, Yixin, Huang, Wenlin
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.08.2006
• Subjects: Antineoplastic agents; antitumor; Biological and medical sciences; gene therapy; IFNγ; Medical sciences; minicircle; nasopharyngeal carcinoma; Otorhinolaryngology. Stomatology; Pharmacology. Drug treatments; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Antineoplastic agent; Human; Nasopharynx cancer; ENT disease; Pharynx disease; Malignant tumor; Nasopharynx carcinoma; Gamma interferon
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-06-0520

Purpose: The aims of this work were to investigate the antitumor effect of IFNγ 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 IFNγ gene and evaluated the effects of minicircle-mediated IFNγ gene transfer on NPC cell lines in vitro and on xenografts in vivo . Results: Relative to p2ΦC31-IFNγ, minicircle-mediated IFNγ gene transfer in vitro resulted in 19- to 102-fold greater IFNγ 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 IFNγ gene transfer on NPC cell lines could be attributed to G 0 -G 1 arrest and apoptosis. Minicircle-mediated intratumoral IFNγ expression in vivo was 11 to 14 times higher than p2ΦC31-IFNγ in CNE-2- and C666-1-xenografted mice and lasted for 21 days. Compared with p2ΦC31-IFNγ treatment, minicircle-IFNγ treatment significantly increased survival and achieved inhibition rates of 77.5% and 83%, respectively. Conclusions: Our data indicate that IFNγ gene transfer exerts antiproliferative effects on NPC cells in vitro and leads to a profound antitumor effect in vivo . Minicircle-IFNγ is more efficient than corresponding conventional plasmids due to its capability of mediating long-lasting high levels of IFNγ gene expression. Therefore, minicircle-mediated IFNγ gene transfer is a promising novel approach in the treatment of NPC.