CYSTEINE PROTEASE INHIBITOR STEFIN A IN MURINE TUMORS DURING TREATMENT BY UKRAIN AND/OR CYCLOPHOSPHAMIDE
KOROLENKO Т.А.1, FALAMEYEVA O.V.1, POTERYAEVA O.N.2, ZHANAEVA S.Y.1, LEVINA O.A.1, NOWICKY J.W.3
1) Laboratory of Cellular Biochemistry, Institute of Physiology RAMS, Novosibirsk, Russia.
2) Institute of Biochemistry RAMS, Novosibirsk, Russia.
3) Ukrainian Anti-Cancer Institute, Vienna, Austria.
Address for correspondence: Prof. T.A. Korolenko, Institute of Physiology RAMS, Novosibirsk-117, 630117 Russia.
Summary: Stefin A (cystatin A) belongs to the family of stefins which are known to be endogenous intracellular inhibitors of cysteine proteases, one of the main tumor suppressors playing an important role as a prognostic factor in several human tumors. Concentration of stefin A has been studied in experimental murine tumors, e.g., LS lymphosarcoma, HA-1 hepatoma and Lewis lung adenocarcinoma, during antitumor treatment. Stefin A concentration was evaluated in tumor tissue, liver, spleen and serum of mice during tumor development as an index of malignization and efficacy of antitumor therapy. Ukrain treatment of tumor-bearing mice (Lewis lung adenocarcinoma) was followed by an increase of inhibitor concentration in liver, but not in tumor tissue. However, in other models, e.g., LS lymphosarcoma and HA-1 hepatoma, stefin A concentration in tumor and liver was not changed. There was a tendency to decrease stefin A concentration in liver and spleen of mice compared with intact animals, in particular in animals bearing LS lymphosarcoma and HA-1 hepatoma. Serum concentration of stefin A increased in HA-1 hepatoma and Lewis lung adenocarcinoma compared with intact mice, and tended to increase during antitumor treatment. The changes, mainly increases, of serum stefin A concentration in tumor-bearing mice were the opposite of the decreases noted in serum cystatin C concentration. In tumor tissue, stefin A level was similar to liver and spleen in all types of murine tumors studied. Stefin A may therefore be used as an index for malignancy and for efficacy of antitumor therapy in experimental murine tumors.