P2.01-091 The Anticancer Effect of Techoic Acids on Lewis Lung Carcinoma Model

Abstract

Ligands of Toll-like receptors (TLR) are often used as adjuvants in order to enhance the immunogenicity of vaccines in therapy of lung cancer. Such ligands are cell wall biopolymers of gram-positive microorganisms Staphylococcus aureus – techoic acids (TAs). They play a significant role as immunomodulators. Nowadays, agents which, in addition to specific effect on cellular and molecular targets of tumor growth and ischemia, possess the ability to inhibit angiogenesis, are attractive for therapeutic angiogenesis-dependent correction of pathological states, which has vascular-dependent outcome. In order to determine possible mechanisms of TAs+PO244 impact on tumor through immune cells we studied primary Lewis lung carcinoma (LLC) culture after the impact of macrophages from LLC-bearing mice at the last stage of carcinogenesis. Both TAs and PO244 were administrated on 8th day after tumor cell inoculation. After the therapy macrophages were contactless co-cultivated with primary LLC culture during 48 h. Mononuclear phagocyte fraction from peritoneal exudate of mice was obtained by standard Pietrangeli's procedure. Apoptotic index and distribution of LLC cells in phases of cell cycle were assessed by flow cytometry. An adhesive potential was assessed with crystal violet. Aforementioned combination revealed in 2-times increasing of LLC cells apoptotic level in comparison with primary LLC cells (without co-culture) and LLC cells under condition of co-cultivation with macrophages from mice without therapy. TAs+PO244 therapy decreased population of LLC cells in proliferative pool (G2/M+S phase) to 40%, whereas control rates were 65% and 60% in LLC cells without co-culture and LLC cells with macrophage co-culture from mice without therapy, respectively. As the adhesive potential inversely correlates with cell ability to migrating, the in vitro data indicated that migration and tumor infiltration can be activate when tumor growing in vivo. We have shown it in combined therapeutic scheme application of TA and PO244 on LLC. Monotherapy by TA stimulates tumor infiltration by lymphocytes insignificantly, whereas in combined therapy with PO244 this parameter is increased 2.4 times (p<0.05). Cytotoxic/cytostatic influence, which was expressed in increasing of apoptotic level and decreasing of cell population of proliferative pool was defined after co-cultivation of macrophages from LLC-bearing mice treated by TAs+PO244 with primary LLC culture. This effect can be one of the possible mechanisms of TAs+PO244 impact on the lung cancer.