Creation of a Model Line of Tumor Cells with Inducible Expression of Adenoviral E1A to Study Its Antiproliferative and Cytotoxic Properties In Vitro and In Vivo

Objective: Over the past decades, gene therapy based on the adenoviral E1A has proven its benefit against several tumor diseases, both in animal models and in clinical studies. It has been shown that in addition to its antiproliferative activity, E1A also can enhance the cytotoxic effect of some anticancer drugs. The use of E1A in combination therapy can solve several problems in clinical oncology, among which the most pressing is the problem of drug-resistance of tumor cells. Methods: This work describes the establishment of a cell model based on human colorectal cancer cells HCT116 and cisplatin-resistant HCT116/C cells with doxycycline-inducible expression of adenoviral E1A. Results and Discussion: We have shown the concentration-dependent and time-dependent dynamics of E1A expression upon doxycycline treatment and shown the antiproliferative effect of adenoviral E1A in the HCT116-E1A and HCT116/C-E1A cells both in vitro using MTT and clonogenic activity assays and in vivo using xenograft mouse models. Thus, as a result of our work, a model was created to explore the antiproliferative and sensitizing properties of E1A in platinum-sensitive and platinum-resistant colorectal cancer cells and to search for new approaches to anticancer therapy both in vitro and in vivo. Conclusions: The resulting cell line is a convenient model for selecting the most promising combinations of cytostatic drugs with E1A-based gene therapy.