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.