PRECLINICAL INVESTIGATION OF THE INFLUENCE OF B. SUBTILIS IMV B-7724 LECTIN ON THE DYNAMICS OF MACROPHAGES FUNCTIONAL ACTIVITY AFTER TRANSPLANTATION OF CHEMOSENSITIVE OR CHEMORESISTANT EXPERIMENTAL TUMORS

Chumak A.V., Fedosova N.І., Cheremshenko N.L., Karaman О.М., Symchych T.V.

• R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine

Aim: to determine the indicators of peritoneal Mph’s functional activity in rats in the dynamics of growth of different Walker carcinosarcoma 256 strains characterized by diverse sensitivity to doxorubicin under the use of doxorubicin or lectin B. subtilis INV B-7724. Object and methods: in the investigation, Wistar rats were used. Sensitive and doxorubicin-resistant (DOX) strains of Walker carcinosarcoma 256 were used as models of tumor growth. DOX was used as the means of chemotherapy; lectin of B. subtilis IMV B-7724 was applied as an immunotherapy. The functional state of peritoneal macrophages (Mph) was assessed based on nitric oxide (NO) production and arginase (Arg) activity; the NO/Arg ratio was calculated. Statistical analyses of the results was done according to generally accepted methods of variation statistics. Results: Regardless of which strain of Walker carcinosarcoma 256 (wild type or DOX-chemoresistant) was transplanted, application of immunotherapy means impede the tumors growth. In the rats transplanted with the doxorubicin-resistant strain of carcinosarcoma Walker 256, decrease in the Mph’s ability to produce NO and increase in arginase activity were the most pronounced: the NO/Arg ratio was 1.8 times (p <0.05) lower than in the intact rats and 1.3 times lower (p < 0.05) comparing with the group of animals bearing the wild strain of the carcinosarcoma. In rats bearing carcinosarcoma, application of bacterial lectin as a means of immunotherapy led to a significant increase in NO production by peritoneal Mph and to a decrease in theirs Arginase activity independently of the tumor sensitivity to chemotherapy. Conclusions: the growth of carcinosarcoma Walker 256 is accompanied with a significant inhibition of Mph antitumor activity. This effect is more pronounced in rats bearing the DOX-resistant strain of the tumor. Application of B. subtilis IMV B-7724 lectin helped to preserve Mph’s type M1 functional phenotype till the late terms of tumor progression, regardless of the experimental tumor’s chemoresistance.