Cysteine cathepsin B and its endogenous inhibitor play an important role in
tumor progression. Increase in
cathepsin B expression and reduced levels of its inhibitors were associated with
tumor malignancy in
breast cancer. The objective of this study was to investigate the effects of a new
therapy combining
vitamin E and placental inhibitor on the level of endogenous
protease inhibitor in sera and
tumor tissues with
mammary cancer. The inhibitor was used in doses of 100 and 200 micrograms per animal for 8 days.
Vitamin E was added after the last treatment with inhibitor and was injected daily in doses of 10 and 20 mg per animal for one mouth. The size and survival time of treated animals as well as
cathepsin B and the inhibitor activity in
tumor and sera before and
after treatment in comparison with the control groups were determined. The activity of
cathepsin B significantly decreased both in
tumor tissues and in sera (P < or = 0.0001).
Cathepsin B activity in
tumor tissue homogenates and in sera decreased two-fold and three-fold, respectively, after the animals were treated with
vitamin E at a dose of 20 mg, and decreased five-fold and 15-fold, respectively, when treated with
vitamin E plus inhibitor in comparison with untreated animals. Endogenous inhibitor activity increased six-fold and 12-fold in the sera and tissue homogenates, respectively, after the animals were treated with 200 micrograms of
cysteine protease inhibitor plus 20 mg of
vitamin E, in comparison with untreated animals. The total cure responses were higher in eight of 10 rats, as compared with untreated animals. The combination of placental inhibitor and
vitamin E resulted in a significant reduction in breast
metastasis and might provide a therapeutic basis for anti-
metastasis therapy.