Biopolym. Cell. 2014; 30(1):61-67.
Molecular Biomedicine
Suppression of tumorigenicity and metastatic potential of melanoma cells by transduction of interferon gene
1Lykhova A. A., 1Kudryavets Yu. I., 1Bezdenezhnykh N. A., 1Semesiuk N. I., 1Adamenko I. N., 1Vorontsova A. L.
  1. R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine
    45, Vasilkivska Str., Kyiv, Ukraine, 01022


The aim of this study was to investigate an inhibitory effect of baculovirus-mediated transduction of the murine interferon-beta gene on mouse melanoma in vitro and in vivo. Methods. Studies were performed on B16 mouse melanoma (MM-4 cell line). Transduction, immunocytochemical and tumor cell biology approaches have been used in this study. Results. Transduction of MM-4 cells by the recombinant baculovirus with IFN-beta gene is accompanied by morphological changes of tumor cells, suppression of cell proliferation, significant inhibition of platting efficiency of cells and their colonies formation in semisolid agar. Moreover, transduction of melanoma MM-4 cells by the baculovirus IFN-transgene leads to inhibition of tumorigenicity and metastatic ability of the cells in vivo. The intravenous administration of recombinant baculovirus vector with IFN gene inhibits growth of metastases induced in the lungs of mice by intravenously injected tumor cells. Conclusions. Transduction of mouse melanoma cells by the recombinant baculovirus with murine IFN-beta gene inhibits their proliferative potential, tumorigenicity and metastatic activity.
Keywords: interferon, recombinant baculovirus, transduction, melanoma cells, tumorigenicity, metastasis.


[1] Wadler S, Schwartz EL. New advences in intrerferon therapy of cancer. Oncologist. 1997; 2(4):254–67.
[2] Abelev GI, Altshtein AD, Belitsky GA, Vasiliev JM, Morozov VA, Myasishcheva NV. Carcinogenesis. Ed. D. G. Zaridze. Moscow: Nauchny mir, 2000; 418 p.
[3] Ferrantini M, Capone I, Belardelli F. Interferon-alpha and cancer: mechanisms of action and new perspectives of clinical use. Biochimie. 2007; 89(6–7):884–93.
[4] Jonasch E, Haluska FG. Interferon in oncological practice: review of interferon biology, clinical applications, and toxicities. Oncologist. 2001; 6(1):34–55.
[5] Qin XQ, Tao N, Dergay A, Moy P, Fawell S, Davis A, Wilson JM, Barsoum J. Interferon-beta gene therapy inhibits tumor formation and causes regression of established tumors in immunedeficient mice. Proc Natl Acad Sci USA. 1998; 95(24):14411–6.
[6] Belzhelarskaya SN. A baculovirus expression system for insect cells. Mol Biol (Mosk). 2002; 36(3):371–85.
[7] Lackner A, Kreidl E, Peter-Vorosmarty B, Spiegl-Kreinecker S, Berger W, Grusch M. Stable protein expression in mammalian cells using baculoviruses. Methods Mol Biol. 2012; 801:75–92.
[8] Airenne KJ, Mahonen AJ, Laitinen O, Yla-Herttuala S. Baculovirus-mediated gene transfer: an evolving new concept. Gene and Cell Therapy. Therapeutic Mechanisms and Strategies. Ed. N. S. Templeton. New York: CRC Press, 2003;181–97.
[9] Vagyna IN, Anopriyenko OV, Zaharuk OA, Gorchev VF, Strokovska LI, Solomko AP. Efficient gene delivery into mammalian cells by baculovirus vector in vitro. Biopolym Cell. 2008; 24(6): 508–12.
[10] Vagyna IN, Anopriyenko OV, Zaharuk EA, Morozova LM, Strokovska LI. Inhibition of growth of mouse melanoma fetal fibroblasts which express IFN-B in vivo. Achievements and problems of genetics, breeding and biotechnology. Ed. V. A. Kunakh. Kyiv: Logos, 2012; Vol. 4:291–7.
[11] Kudryavets YuI. Mouse melanoma cell line spontaneously producing C-type virions. Mat. 7th Conf. «Problems of Microbiology and Virology». Riga: Zinatne, 1977;162–3.
[12] Skivka L, Susak Y, Trompak O, Kudryavets Yu, Bezdeneznikh N, Semesiuk N, Lykhova O. The effect of monotherapy and combined therapy with NSC-631570 (ukrain) on growth of lowand high-metastasizing B16 melanoma in mice. J Oncol Pharm Pract. 2011; 17(4):339–49.
[13] Vorontsova AL, Kudryavets YuI, Fadeev VA, Balitskii KP. Antimetastatic effects of interferon in the surgical removal of experimental tumors. Exp Oncol. 1983; 5(5):45–9.
[14] Gluzman DF, Abramenko IV, Skliarenko LM, Kryachok IA, Nadgornaya VA. Diagnosis of leukemia. Atlas and practical guide. Kiev: Morion, 2000; 224 p.
[15] Vega-Avila E, Pugsley MK. An overview of colorimetric assay methods used to assess survival or proliferation of mammalian cells. Proc West Pharmacol Soc. 2011; 54:10–4.
[16] Hamburger AW, Lurie KA, Condon ME. Stimulation of anchorage-independent growth of human tumor cells by interleukin 1. Cancer Res. 1987; 47(21):5612–5.
[17] Zhang X, Xu L, Yu Q. Cell aggregation induces phosphorylation of PECAM-1 and Pyk2 and promotes tumor cell anchorageindependent growth. Mol Cancer. 2010; 9:7.