Suppression of proliferation, tumorigenicity and metastasis of lung cancer cells after their transduction by interferon-beta gene in baculovirus vector

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2015-02, Vol.71 (2), p.318-326
• Main Authors: Lykhova, Alexandra A., Kudryavets, Yuri I., Strokovska, Ludmila I., Bezdenezhnykh, Natalia A., Semesiuk, Nadiia I., Adamenko, Inna N., Anopriyenko, Olga V., Vorontsova, Ada L.
• Format: Article
• Language: English
• Subjects: Animals; Autographa californica; Baculoviridae - genetics; Baculovirus; Carcinoma, Lewis Lung - metabolism; Cell Line, Tumor; Cell Proliferation; Genetic Therapy - methods; Genetic Vectors; Immunohistochemistry; Interferon-beta; Interferon-beta - genetics; Interferon-beta - metabolism; Lewis lung carcinoma cells; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Metastasis; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Neoplasm Transplantation; Nuclear polyhedrosis virus; Phenotype; Recombinant baculovirus; Tumorigenicity; Vesicular stomatitis virus
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2014.10.029

•We studied changes of biological parameters of LL/rBV/IFN-beta cells.•Inhibition of proliferation and сolony-forming activity was observed in LL/rBV/IFN cells.•Suppression the tumorigenicity and metastases was found in LL/rBV/IFN-beta cells.•Inhibition of proliferation and tumorigenicity was not observed in LL/rBV cells. Gene therapy represents an interesting alternative treatment for cancers. Interferon-beta is well known as a multifunctional cytokine that provides antiviral, antiproliferative, antiangiogenic and immunomodulating effects. For this reason introduction of this cytokine gene in baculovirus vector is seen as a rather promising tool for anticancer therapy. Investigation of biological behavior in vitro and in vivo of lung cancer cells modified by interferon-beta gene which was introduced into the cells in vitro with baculovirus vector. Studies were performed on mouse Lewis lung carcinoma cells as the tumor model (LL cell line). Transductions of cells by recombinant baculoviruses, in vitro and in vivo analysis of tumor cell biology and immunocytochemical method have been used. The study of various in vitro biological parameters of LL cancer cells transduced by recombinant baculovirus with interferon gene demonstrated that the transduction of cells is accompanied by significant inhibition of their proliferation and ability to form colonies in semisolid agar. Also, transduction of LL cells with interferon gene inhibited their tumorigenicity, i.e. the ability to cause formation of tumors and metastases in lungs of mice in vivo. Anti-tumor activity of recombinant interferon is realized via high level of its local production in tumors, induced by LL carcinoma cells, transduced with recombinant interferon-beta gene. Recombinant baculovirus without interferon gene did not influence significantly on tumorigenicity and metastatic ability of lung cancer cells. Introduction of interferon-beta gene in Lewis lung carcinoma cells in vitro in recombinant baculovirus leads to inhibition of their proliferation potential and malignant behavior in vitro, tumorigenicity and metastatic activity in vivo.