Effects of combined in vivo treatment of transplantable solid mammary carcinoma in wistar rats using vitamin E and cysteine peptidase inhibitors from human placenta.

Abstract

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.