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

Authors' Affiliations: ¹ State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, PR China; ² Department of Endorinology, Chengdu Army General Hospital, Chengdu, PR China; and ³ Institute of Microbiology, Chinese Academy of Science, Beijing, PR China

Requests for reprints: Wenlin Huang, Cancer Center, Sun Yat-sen University, Guangzhou 510060, PR China. Phone: 86-20-8734-3178; Fax: 86-20-8734-3146; E-mail: wl_huang{at}hotmail.com.

Purpose: The aims of this work were to investigate the antitumor effect of IFN 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 gene and evaluated the effects of minicircle-mediated IFN gene transfer on NPC cell lines in vitro and on xenografts in vivo.

Results: Relative to p2C31-IFN, minicircle-mediated IFN gene transfer in vitro resulted in 19- to 102-fold greater IFN 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 gene transfer on NPC cell lines could be attributed to G₀-G₁ arrest and apoptosis. Minicircle-mediated intratumoral IFN expression in vivo was 11 to 14 times higher than p2C31-IFN in CNE-2- and C666-1-xenografted mice and lasted for 21 days. Compared with p2C31-IFN treatment, minicircle-IFN treatment significantly increased survival and achieved inhibition rates of 77.5% and 83%, respectively.

Conclusions: Our data indicate that IFN gene transfer exerts antiproliferative effects on NPC cells in vitro and leads to a profound antitumor effect in vivo. Minicircle-IFN is more efficient than corresponding conventional plasmids due to its capability of mediating long-lasting high levels of IFN gene expression. Therefore, minicircle-mediated IFN gene transfer is a promising novel approach in the treatment of NPC.