Lykhova O. Phenotypic characteristics of tumor cells in vitro and in vivo after their transduction by interferon-beta gene in recombinant baculovirus vector

The thesis is devoted to investigation of influence of recombinant baculovirus with interferon-beta gene on phenotypic characteristics of tumor cells in vitro: morphology, growth, cytogenetic characteristics and expression of proteins associated with proliferative activity, cell cycle regulation, epithelial-mesenchymal transition, invasiveness, migration potential. Tumorigenicity and metastatic potential of tumor cells after their transduction by baculovirus vector with interferon-beta gene was investigated in experiments in vivo. Transduction of melanoma cells (MM-4 cell line) and Lewis lung carcinoma cells (cell line LL) by baculovirus vector with mouse interferon-beta gene leads to significant changes in their growth characteristics: inhibition of cell proliferation, reduction of their colony forming activity in semisolid agar and their ability to grow in medium without serum. Production of recombinant interferon-beta in MM-4 and LL cells is accompanied with increase the expression of oncosupressor proteins p19ARF and p21WAF1, decrease the expression of N-cadherin in MM-4 cells, increase the number of E-cadherin+ LL cells and that indicates about inhibition of invasiveness and migration potential of these cells. Transduction of MM-4 and LL cells by baculovirus vector with interferon-beta gene in vitro inhibits their ability to form solid tumors and metastases in the lungs of mice.