EFFECT OF DIFFERENT BIOLOGICAL RESPONSE MODIFIERS ON GROWTH AND METASTASIZING OF MURINE LEWIS LUNG ADENOCARCINOMA
ZHANAEVA S.J.A.1, FALAMEYEVA O.V.1, FILATOVA T.G.1, GONCHAROVA I.A.1, SUKHENKO T.G.2, KOLESNIKOVA O.P.2, KALEDIN V.l.3, KOROLENKO Т.А.1, NOWICKY W.M.4
1) Institute of Physiology RAMS, Novosibirsk, Russia.
2) Institute of Clinical Immunology RAMS, Novosibirsk, Russia.
3) Institute of Cytology and Genetics RAS, Novosibirsk, Russia.
4) Ukranian Anti-Cancer Institute, Vienna, Austria.
Address for correspondence: S.Y. Zhanaeva, Laboratory of Cellular Biochemistry, Institute of Physiology, Russian Academy
of Medical Sciences, ul. Timakova 4, 630117 Novosibirsk, Russia.
Summary: Biological response modifiers are important drugs used in oncology and among them are the novel antitumor drug Ukrain and the more studied (1 ->3)-beta-D-glucans. The aim of this study was to evaluate in vivo the antitumor and antimetastatic capacity of Ukrain and (1 ->3)-beta-D-glucans in the experimental murine Lewis lung solid tumor adenocarcinoma, metastasizing to lung and relatively resistant to cyclophosphamide therapy Administration of Ukrain was shown to reveal antimetastatic effects in the murine Lewis lung adenocarcinoma model, possibly due to Ukrain's capacity to stimulate macrophages (according to increased serum chitotriosidase activity as an index of macrophage stimulation). The combination of cyclophosphamide plus Ukrain was also shown to be effective: 20% of mice developed lung metastases and 80% did not have metastases, compared with the control group, where 100% of mice developed metastases. Ukrain was shown to significantly restore serum aspartate transaminase (AST) activity, decreasing toxic effects of tumor bearing in mice with Lewis lung adenocarcinoma. Combined therapy with carboxymethylated (1 ->3)-beta-D-glucan (CMG) plus cyclophosphamide inhibited tumor growth and decreased the frequency of lung metastases. Cyclophosphamide alone inhibited the growth of primary tumor by 62%, whereas chitocarboxymethylated (1 ->3)-beta-D-glu-can (chitoCMG) was ineffective in primary tumor growth inhibition. Both glucans were found to stimulate the release of tumor necrosis factor (TNF)-alpha from peritoneal murine macrophages. Serum chitotriosidase activity as a biochemical marker of macrophage stimulation in mice treated with Ukrain, CMG and chitoCMG increased compared with intact mice.